ORIGINAL ARTICLE Annals of Gastroenterology (2014) 27, 1-14

In silico analysis identifies common between five primary gastrointestinal cancer sites with potential clinical applications

Subhankar Chakraborty University of Nebraska Medical Center, Omaha, NE, USA

Abstract Background Previous studies have investigated differential expression in gastrointes- tinal (GI) epithelial cancers by microarray. The aim of the present study was to use data from the Oncomine database to identify genes that share a similar differential expression in two or more primary GI cancer sites. Methods Five thousand of the most differentially expressed genes in epithelial cancers (com- pared to normal tissue) arising in the pancreas, liver, stomach, esophagus or colorectum were identified (1,000 per primary site) from Oncomine. Using Venn diagrams, genes common to two or more primary GI sites were identified. Functional and pathway analysis was performed on genes that were similarly expressed in ≥3 of the five areas of the GI tract. Results Forty six studies comprising 5,876 samples were included. Overall, 90.6% genes were unique to the respective primary sites, 7.4% shared between two GI primary sites, 1.8% between three and 0.2% between four GI primary sites. Pancreatic and hepatocellular cancers (HCC) shared most number of upregulated genes (N=66) while HCC and gastric cancer shared most downregulated genes (N=59). Genes encoding enzymes comprised the most commonly shared genes between GI primary sites (30.4% of upregulated and 63.2% of downregulated genes). Those genes that were shared between three or more GI primary sites also showed significant differential expression in the same direction in other non-GI cancers. Conclusion The present study has identified several genes that show similar differential expres- sion in cancers arising from two or more sites in the GI tract. These genes can be potentially useful as novel therapeutic targets. Keywords Oncomine, pathway, network, database, cancer, gastrointestinal, therapy Ann Gastroenterol 2014; 27 (2): 1-14

Introduction count for nearly 17.5% of all new cancer cases and about 25% of cancer related deaths in 2013. While there are numerous The Oncomine database is one of the largest collections of studies that have investigated the global gene expression in microarray data. The current research edition has 715 datas- various gastrointestinal (GI) cancers compared to normal GI ets with 86,733 samples. According to the American Cancer tissue, there are differences in the results from study to study. Society, cancers of the digestive tract comprise about 290,000 Thus, analysis of results from multiple studies provides the new cancers each year while accounting for nearly 145,000 opportunity to get a more accurate picture of differential gene cancer related deaths annually. Thus they are expected to ac- expression in cancer tissues. The GI tract is embryologically derived from the endoderm with the esophagus and stomach Department of Internal Medicine, University of Nebraska Medical derived from the foregut, duodenum from the foregut and Center, Omaha, NE midgut, liver from the ventral mesentery, pancreas from the septum transversum, transverse and ascending colon from Conflict of Interest: None the midgut and the transverse colon and rectum from the Correspondence to: Subhankar Chakraborty, M.D., Ph.D., hindgut. If we could identify a set of genes that are common Department of Internal Medicine, University of Nebraska Medical between cancers arising from multiple GI sites, this would Center, Omaha, NE- 68198-2055, USA, Tel.: +978 810 5992, help identify pathways and in turn targets for therapy of GI e-mail: [email protected] malignancies. The Oncomine database provides us the op- Received 20 November 2013; accepted 6 January 2014 portunity to test this hypothesis owing to the large number

© 2014 Hellenic Society of Gastroenterology www.annalsgastro.gr 2 S. Chakraborty of samples available for analysis. In this study, we compared Results gene expression between epithelial cancers arising from five different GI primary sites (pancreas, liver, esophagus, stomach A total of 5,000 genes (1,000 genes per primary GI site) and colorectum). We discovered that there were multiple genes were included in the analysis. For each primary site, we identi- common to at least three and four GI primary sites but none fied 500 genes that were upregulated and 500 that were most to all five primary sites. downregulated in majority of the included studies. There were fifteen studies comparing colorectal cancer to normal colon, seven comparing esophageal cancer (includes both squamous Methods and adenocarcinoma) to normal esophagus, seven on gastric cancer, eight on hepatocellular (HCC) and nine comparing pancreatic cancer to respective normal tissue. These studies The Oncomine database (www.oncomine.org ) was que- included 2208, 514, 1408, 1324 and 422 samples respectively. ried for studies comparing normal tissue from a part of the To compare gene expression between the five primary GI GI tract to tissue from an epithelial malignancy arising from sites (pancreas, liver, stomach, esophagus and colorectum) the same tissue. All studies in the database which compared and in turn identify genes that were common between two or gene expression in GI cancer tissue to the corresponding more primary sites, we used the VENNTURE Venn diagram normal tissue were included. For instance there were fifteen tool. Separate comparisons were made for upregulated (Fig. studies involving 2,208 samples that had compared gene 1) and downregulated genes (Fig. 2). expression in colorectal cancer to the corresponding normal tissue. The Oncomine database allows us to compare gene expression across multiple studies to identify the genes that Upregulated genes are differentially over or under expressed in majority of the studies. Only those genes with P-value <0.05 were included. The first 500 most over and 500 most under expressed genes Table 1 shows the number of genes that were commonly for each primary site were included in the analysis. Five pri- upregulated in epithelial cancers arising from two or more mary sites in the GI tract, i.e. esophagus, stomach, pancreas, primary GI sites (the genes that are differentially upregulated liver, and colorectum, were included in the study. To identify in GI cancers can be found in Supplementary File 1). Among genes that were commonly expressed between different GI the five GI sites, gastric cancer shared the most number of malignancies, we used VENNTURE, a freely available tool to upregulated genes with the other four sites (only 51.8% of compare genes among up to six groups (http://www.irp.nia. upregulated genes were unique to gastric cancer). In com- nih.gov/branches/lci/nia_bioinformatics_software.html). To parison, HCC shared the least number of upregulated genes investigate the function of a given gene we used the PANTHER with other sites (71.2% genes were unique to HCC). database (http://www.pantherdb.org/). Interactions of one Pancreatic cancer and HCC had sixty six (13.2%) of up- or more genes with other genes were investigated using the regulated genes in common, making them the two cancers GeneMania online tool (http://genemania.org/). To investigate most similar in this category. They were followed by pancre- chemicals targeting a particular gene product, we used the atic/esophageal cancer with 31 (6.2%) and esophageal/gastric STITCH database (http://stitch.embl.de/). cancer with 29 (5.8%) genes in common.

A Total number of genes Stomach B By Sequence Stomach Liver Liver

Pancreas Pancreas

Colorectal Colorectal

Esophagus Esophagus

Figure 1 Venn diagram analysis of genes upregulated in five primary gastrointestinal cancer sites. A color represents a particular primary site of GI cancer- for instance, pink is Pancreas, green is for liver, light blue for colorectum, red for stomach and dark blue for esophagus. In Panel A, Venn diagram method has been used to identify the number of genes that are shared between two or more cancers. For instance, cancers arising in the pancreas and liver share 66 common upregulated genes while 306 genes are unique to the pancreas. In Panel B, we have sequence numbers corresponding to the column numbers in Supplementary File 1. Refer to the corresponding column number for the names of specific genes. For instance, the 66 upregulated genes common between pancreatic and liver cancer are in column 13

Annals of Gastroenterology 27 Commonalities in transcriptome of GI malignancies 3

A By total number of genes Stomach B By Sequence Stomach Liver Liver

Pancreas Pancreas

Colorectal Colorectal

Esophagus Esophagus

Figure 2 Venn diagram analysis of genes downregulated in five primary GI cancer sites. A color represents a particular primary site of GI cancer- for instance, pink is Pancreas, green is for liver, light blue for colorectum, red for stomach and dark blue for esophagus. In Panel A, Venn diagram method has been used to identify the number of genes that are shared between two or more cancers. For instance, cancers arising in the pancreas and liver share 25 common downregulated genes while 378 genes are unique to the pancreas. In Panel B, we have sequence numbers corresponding to the column numbers in Supplementary File 2. Refer to the corresponding column number for the names of specific genes. For instance, the 25 downregulated genes common between pancreatic and liver cancer are in column 13

When we examined three primary GI sites that shared down-regulated in different primary GI cancers, we next common upregulated genes, esophageal, gastric and colorec- sought to investigate the pathways that these common genes tal cancer with 18 common genes (3.6% of total) were first. represented. Pancreatic, HCC and gastric cancer with 10 common genes We chose genes that were shared between three or more GI (2% of total) were second. primary sites for this analysis. We hypothesized that this would When we examined over expressed genes common to four lead to an enrichment of genes (and therefore pathways) that primary GI sites, the pancreas, liver, stomach and esophageal were key in the development of cancer in GI and potentially cancers had three genes in common (0.6% of total). There in other non-GI cancers as well. To assign biological function was no gene upregulated in all five primary sites. to genes, we used the PANTHER program. Overall, we were able to identify the function of a gene in 90% of upregulated and 69% of downregulated genes that were common in Downregulated genes three or more primary GI sites. We divided these genes into eleven functional groups, i.e. transporter , enzymes, Gastric cancer shared the most number of downregulated cytokines and growth factors, proteins (Excluding enzymes) genes with other cancers with only 60.8% unique genes, while involved in DNA replication, transcription factors, binding pancreatic cancer shared the least (75.6% unique genes) (Table proteins, proteins involved in translation, chaperones, immu- 1). The list of genes that are differentially downregulated in nity associated proteins, structural proteins, and others (that GI cancers can be found in Supplementary File 2. did not fit into any of the previous ten groups). As a group, With fifty nine genes (11.8% of total) commonly down- enzymes comprised the bulk of genes differentially expressed regulated genes, HCC and gastric cancer were most similar, in cancer cells, making up 30.4% of upregulated and 63.2% of followed by pancreatic/gastric cancer with 28 (5.6% of total) downregulated genes (Supplementary Fig. 1 and 2). Binding and pancreatic cancer/HCC with 25 (5% of total) genes in proteins were the second most common group, accounting common. for 19.6% of upregulated and 13.2% of downregulated genes. Gastric cancer, HCC and colorectal cancer had twenty The functional classification of the genes commonly up or genes in common making them the most similar trio. When downregulated in three or more primary GI cancer sites is comparing commonly downregulated genes in four primary summarized in Table 2. GI sites, pancreatic, HCC, gastric and colorectal cancer had In order to investigate the cellular pathways regulated by six genes in common making them the most similar quartet. genes common to three or more GI cancers, we used the Gen- There was no gene common to all five primary GI sites. eMania online program to investigate the interactions of these genes with other genes. For the upregulated genes, we noticed interactions with cell cycle regulators, Ras and Rho GTPases Functional classification of genes shared and components of the extracellular matrix. These genes were between different primary GI sites also involved in pathways that regulated cell division, adhesion, motility and assembly of the cell junctions (Supplementary Having identified the genes that were commonly up- or Fig. 3). The genes that were downregulated were involved

Annals of Gastroenterology 27 4 S. Chakraborty

Table 1 Summary of common gene expression between two or more primary gastrointestinal primary cancer sites

Number of genes

Upregulated Downregulated

Number of genes Percentage of total genes Number of genes Percentage of total genes One primary site Pancreas only 306 61.2 378 75.6 Liver only 356 71.2 331 66.2 Stomach only 259 51.8 304 60.8 Colorectal only 316 63.2 330 66.0 Esophagus only 339 67.8 331 66.2 Two or more primary sites I. Two primary sites Pancreas and colorectal 16 3.2 20 4.0 Pancreas and stomach 24 4.8 28 5.6 Pancreas and esophagus 31 6.2 10 2.0 Pancreas and liver 66 13.2 25 5.0 Liver and colorectal 1 0.2 1 0.2 Liver and stomach 23 4.6 59 11.8 Liver and esophagus Esophagus and stomach 29 5.8 15 3.0 Esophagus and colorectal 18 3.6 5 1.0 II. Three primary sites Pancreas, esophagus, stomach 9 1.8 2 0.4 Pancreas, esophagus, liver 3 0.6 2 0.4 Pancreas, esophagus, colorectal 5 1.0 1 0.2 Pancreas, liver, stomach 10 2.0 12 2.4 Esophagus, stomach, liver 4 0.8 1 0.2 Esophagus, stomach, colorectal 18 3.6 5 1.0 Stomach, liver, colorectal 4 0.8 20 4.0 Esophagus, liver, colorectal 1 0.2 2 0.4 Pancreas, liver, colorectal 0 0.0 3 0.6 III. Four primary sites Pancreas, liver, stomach, colorectal 0 0.0 6 1.2 Pancreas, liver, stomach, esophagus 3 0.6 0 0.0 Liver, stomach, esophagus, colorectal 1 0.2 1 0.2 All 5 primary sites 0 0.0 0 0.0 in pathways that inhibited cell motility and cell growth, and Table 2 Functional classification of genes common between three regulated metabolism (including steroid, cholesterol, alcohol or more primary gastrointestinal malignancies metabolism) and cellular biosynthesis (synthesis of glycolipids, Percentage of genes lipoproteins and phosphatidylinositol). These genes (and their interacting partners) included several enzymes important in Functional group Upregulated Downregulated metabolic pathways including transferases, hydrolases and Enzyme 30.4 63.2 oxidoreductases (Supplementary Fig. 4). Binding proteins 19.6 13.2 Next, we investigated whether the genes that were most 10.9 2.6 commonly over or under expressed in GI cancers were also Structural 8.7 0.0 similarly expressed in non-GI cancers. For this, we chose genes that were common to four or more GI sites. Like before, we DNA replication 6.5 2.6 felt this would give us the best enrichment of genes commonly Chaperone 6.5 0.0 expressed in GI malignancies. Thus, we examined the expres- Transporter 4.3 7.9 sion of TMEM220, ACADVL, RNF222, ZZEF1, RILP, and G Cytokine/growth factor 4.3 0.0 protein suppressor (GPS)2 all of which were downregulated in Translation protein 4.3 5.3 pancreatic, HCC, gastric and esophageal cancer compared to Immunity 4.3 2.6 the corresponding normal tissue. Oncomine has twenty one Other 0.0 2.6 categories of primary tumor sites. We analyzed the percentage

Annals of Gastroenterology 27 Commonalities in transcriptome of GI malignancies 5

squamous cell cancer [4] and adrenocortical carcinomas [5]. RILP (Rab7-interacting lysosomal protein) has been shown to be important for lysosome trafficking, which in turn was found to be a key determinant of tumor cell invasion [6]. GPS2 downregulation by siRNA stimulated proliferation in breast cancer cells, suggesting that it is a tumor suppressor [6]. There is currently no literature on the role of TMEM220, RNF222 and ZZEF1 in cancer. Finally, we investigated the possibility of identifying novel inhibitors for the above identified genes. As an example, we chose UBE2C. The STITCH online database identifies chemi- cals that have or predicted to have an interaction with a given protein. These are linked to databases like PubChem where further information regarding the compound can be obtained. For UBE2C, there were two chemicals identified (Fig. 3).

Discussion

In the present study, we compared five hundredof the most over- and under-expressed genes in five primary GI sites. The percentage of genes that were shared between two or more GI cancers ranged between 29-48% for the upregulated genes and 24-39% for the downregulated genes. About 7.5% of the five Figure 3 Identification of potential inhibitors of target genes using thousand genes were common to two primary GI sites, 1.8% STITCH (http://stitch.embl.de/) online tool. Interaction of UBE2C to three primary GI sites and 0.2% to four primary GI sites. with other proteins; thicker lines represent stronger interaction. Genes encoding for enzymes, receptors and nucleic acid binding Protein-protein interactions are in blue, chemical protein interactions in green and interactions between chemicals in red. Thus, k11 (CID proteins were most commonly upregulated while those for en- 16731782) and QqQ (PubChem CID 2772579) are inhibitors of UBE2C zymes, receptors, nucleic acid binding proteins and cytoskeletal proteins were most commonly downregulated in GI cancers. Oncomine has been used previously to investigate the of primary sites where each gene was underexpressed compared differential expression of specific genes in cancer including to the corresponding normal tissue. The resulting percentage pore domain potassium channels, calcium channels, and RGS was underexpression in 100%, 87.5%, 100%, 75%, 100%, 100% (regulators of G protein signaling) family of proteins [7-9]. of primary non-GI cancer tissues compared to the correspond- Rhodes and colleagues in 2004 used Oncomine to identify a ing normal tissue. For this analysis, we chose a P-value of transcriptional profile that was common to most cancers and 0.0001, a fold change of 2 or more and included top 10% of all suggested that this likely reflected a common set of genes that genes. For GPS2 we chose a P-value of 0.05. From among the were differentially overexpressed in most malignancies (com- upregulated genes, we chose COL4A1 (upregulated in HCC, pared to the normal tissue) [10]. Oncomine has also been used gastric, esophageal and colorectal cancer), UBE2C, OLFML2B to identify gene signatures to classify tumors [7,8,11]. and ANP32E (upregulated in pancreatic, HCC, gastric and In this study, we focused on GI malignancies. We used the esophageal cancer). They were significantly upregulated in advantages of large sample size and ability to compare gene cancer tissues compared to corresponding normal tissues in expression across multiple studies to identify the top 1000 90.5%, 95%, 100% and 76% of studies. Further, we searched the differentially expressed genes in different GI primary sites. literature for role of the aforementioned genes in both GI and We then investigated genes that were common between two non-GI malignancies. UBE2C was the most upregulated gene or more of five GI primary sites. Once these were identified, in primary colon cancer and liver metastases in one study [1]. It we further investigated the pathways they are involved it. The was also upregulated nearly 150-fold in human thyroid cancer genes identified in this study could potentially be targeted for cell lines and in anaplastic thyroid cancer tissues compared to development of novel therapeutics. We hypothesize that the the non neoplastic thyroid cells [2]. Short interfering RNAs resultant inhibitors would potentially be effective in malignan- (siRNAs) against UBE2C when combined with inhibitors of cies arising from different GI primary sites. An interesting the DR5/TRAIL pathway induced cell death in the cancer, observation in the present study was that genes encoding but not in normal cells [3]. No data exists on functional role enzymes were the most differentially altered in cancer cells of OLFML2B, ANP32E in cancer. Among the downregulated compared to normal cells. This underlines the importance genes, ACADVL (Acyl coenzyme-A dehydrogenase very long of alterations in cellular metabolism in cancer. chain) expression was significantly downregulated in cervical Previous studies have used microarray technology to

Annals of Gastroenterology 27 6 S. Chakraborty identify therapeutic targets that were then verified by biologic In our study, we have not only identified genes that have studies. Turner and colleagues for instance, used high resolu- previously been shown to play a role in GI malignancies tion microarray based comparative genomic hybridization (e.g. UBE2C) but also new ones about whom little is known to identify 40 genes that were significantly over expressed in regarding their role in cancer (e.g. TMEM220 and RNF222). triple negative breast cancer (TNBC). Of these, the authors Further studies are needed to investigate the role of these demonstrated in vitro inhibition of breast cancer cell growth genes in the pathogenesis of GI cancers and as diagnostic, using an inhibitor to FGFR2, one of the oncogenes identified prognostic or therapeutic targets. as being upregulated in TNBC [12]. Saito and co-workers used Thus, in summary we have used the Oncomine database gene microarray to identify CD32 and CD25 as two genes that to compare differential gene expression between different were highly expressed in leukemia-specific stem cells. The GI cancers to identify common genes that in turn could be expression of these genes was however suppressed in normal useful as targets for diagnosis and therapy. hematopoietic stem cells [13]. These studies illustrate how mi- croarray studies are very helpful to sift through large amounts of genetic information to identify targets that are commonly over or under expressed. The translation of genomic studies References into therapeutic discoveries has been discussed in a recent article by Crews and colleagues [14]. The authors discuss how 1. Takahashi Y, Ishii Y, Nishida Y, et al. Detection of aberrations of using data available in the public domain, researchers have ubiquitin-conjugating enzyme E2C gene (UBE2C) in advanced identified genes and in turn potential drugs that targeted the colon cancer with liver metastases by DNA microarray and two- differentially expressed genes. We used the STITCH database color . Cancer Genet Cytogenet 2006;168:30-35. 2. Lee JJ, Au AY, Foukakis T, et al. Array-CGH identifies cyclin D1 and identified two potential inhibitors of UBE2C, one of the and UBCH10 amplicons in anaplastic thyroid carcinoma. Endocr genes shared between multiple GI cancers and upregulated Relat Cancer 2008;15:801-815. in cancer cells. Further in vitro studies are needed to confirm 3. Wagner KW, Sapinoso LM, El-Rifai W, et al. Overexpression, the inhibitory activity of this drug on cancer cells. genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin. Oncogene 2004;23:6621-6629. 4. Pan Z, Chen S, Pan X, et al. Differential gene expression identified Summary Box in Uigur women cervical squamous cell carcinoma by suppression subtractive hybridization. Neoplasma 2010;57:123-128. 5. Soon PS, Libe R, Benn DE, et al. Loss of heterozygosity of 17p13, What is already known: with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors. Ann Surg 2008;247:157- • Different cancers have similarities in gene expres- 164. 6. Steffan JJ, Cardelli JA. Thiazolidinediones induce Rab7-RILP- sion patterns MAPK-dependent juxtanuclear lysosome aggregation and reduce • Gastrointestinal (GI) tract arises from the endoderm tumor cell invasion. Traffic 2010;11:274-286. • Multiple studies comparing gene expression in nor- 7. Williams S, Bateman A, O’Kelly I. Altered expression of two- mal tissue vs. cancer arising from different parts of Pore domain potassium (K2P) channels in cancer. PLoS One the GI tract have been performed, many of which 2013;8:e74589. 8. Chen R, Zeng X, Zhang R, et al. Cav1.3 channel α1D protein is are archived in the Oncomine database overexpressed and modulates androgen receptor transactivation in prostate cancers. Urol Oncol 2013; doi: 10.1016/j.urolonc. What the new findings are: 9. Sethakorn N, Dulin NO. RGS expression in cancer: oncomining the cancer microarray data. J Recept Signal Transduct Res 2013;33:166- 171. • Of the 5,000 most commonly differentially expressed 10. Rhodes DR, Yu J, Shanker K, et al. Large-scale meta-analysis genes in GI cancer arising from five different primary of cancer microarray data identifies common transcriptional sites, nearly 7.4% were common to two primary profiles of neoplastic transformation and progression. Proc Natl sites, 1.8% to three and 0.2% to four primary GI sites Acad Sci U S A 2004;101:9309-9314. • Subset analysis reveals that among the genes com- 11. Rhodes DR, Yu J, Shanker K, et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. mon to three or more GI cancers, those that are part Neoplasia 2004;6:1-6. of pathways regulating cell cycle, adhesion, motility 12. Turner N, Lambros MB, Horlings HM, et al. Integrative molecular and cell junction formation were upregulated while profiling of triple negative breast cancers identifies amplicon those that inhibited motility, growth and metabolism drivers and potential therapeutic targets. Oncogene 2010;29:2013- were downregulated 2023. • Genes that were expressed in cancers arising from 13. Saito Y, Kitamura H, Hijikata A, et al. Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia three or more GI sites were also differentially ex- stem cells. Sci Transl Med 2010;2:17ra9. pressed in a similar direction in most of the non-GI 14. Crews KR, Hicks JK, Pui CH, Relling MV, Evans WE. malignancies Pharmacogenomics and individualized medicine: translating science into practice. Clin Pharmacol Ther 2012;92:467-475.

Annals of Gastroenterology 27 Commonalities in transcriptome of GI malignancies 7

Appendix

Gastric cancer Pancreatic cancer

Enzyme Enzyme Nucleic acid binding protein Receptor protein Transcription factor Enzyme modulator Receptor protein Nucleic acid binding protein Transporter Transporter Enzyme modulator Transcription factor Signaling protein Signaling protein Cytoskeletal protein Cytoskeletal protein Immunity related Calcium binding protein ECM protein ECM protein Carrier protein Calcium binding protein Immunity related Cell adhesion protein Membrane traffic protein Carrier protein Cell junction protein Chaperone Transmembrane binding … Membrane traffic protein Cell adhesion protein Cell junction protein Storage protein Transmembrane binding … Chaperone Storage protein Viral protein Surfactant Surfactant Viral protein

0 10 20 30 40 0 10 20 30 40

Esophageal cancer Hepatocellular cancer

Enzyme Enzyme Cytoskeletal protein Receptor protein Enzyme modulator Nucleic acid binding protein Nucleic acid binding protein Transcription factor Transcription factor Transporter Receptor protein Enzyme modulator Transporter Immunity related Signaling protein Carrier protein Membrane traffic protein Cell adhesion protein Calcium binding protein Signaling protein Carrier protein ECM protein Immunity related Calcium binding protein Cell adhesion protein Cytoskeletal protein Chaperone Chaperone ECM protein Membrane traffic protein Cell junction protein Cell junction protein Transmembrane binding protein Surfactant Viral protein Viral protein Surfactant Transmembrane binding … Storage protein Storage protein 0 10 20 30 40 50 0 10 20 30 40 50

Colorectal cancer

Enzyme Nucleic acid binding protein Receptor protein Transporter Transcription factor Enzyme modulator Signaling protein Cytoskeletal protein Calcium binding protein Chaperone Immunity related Carrier protein ECM protein Membrane traffic protein Cell adhesion protein Transmembrane binding protein Cell junction protein Viral protein Surfactant Storage protein

0 10 20 30 40 50

Supplementary Figure 1 Bar graph showing classification of the five hundred upregulated genes in a given gastrointestinal primary malignancy by their function

Annals of Gastroenterology 27 8 S. Chakraborty

Gastric cancer Pancreatic cancer

Enzyme Enzyme Nucleic acid binding protein Receptor protein Transcription factor Signaling protein Enzyme modulator Enzyme modulator Receptor protein Nucleic acid binding protein Cytoskeletal protein Transporter Signaling protein Cell adhesion protein Transporter Cytoskeletal protein Immunity related Transcription factor Cell adhesion protein ECM protein ECM protein Immunity related Carrier protein Calcium binding protein Calcium binding protein Carrier protein Chaperone Membrane traffic protein Membrane traffic protein Cell junction protein Surfactant Chaperone Cell junction protein Surfactant Transmembrane binding protein Transmembrane binding … Viral protein Viral protein Storage protein Storage protein

0 5 10 15 20 25 30 0 5 10 15 20 25 30

Percentage of genes Percentage of genes

Esophageal cancer Hepatocellular cancer Enzyme Enzyme Nucleic acid binding protein Nucleic acid binding protein Receptor protein Receptor protein Enzyme modulator Enzyme modulator Signaling protein Transcription factor Transporter Signaling protein Transcription factor Transporter ECM protein Cytoskeletal protein Cell adhesion protein Cell adhesion protein Immunity related Immunity related Cytoskeletal protein ECM protein Chaperone Membrane traffic protein Membrane traffic protein Calcium binding protein Carrier protein Chaperone Calcium binding protein Carrier protein Surfactant Cell junction protein Cell junction protein Transmembrane binding protein Transmembrane binding … Surfactant Viral protein Viral protein Storage protein Storage protein

0 5 10 15 20 25 30 0 5 10 15 20 25 30

Percentage of genes Percentage of genes

Colorectal cancer

Enzyme Nucleic acid binding protein Transcription factor Enzyme modulator Transporter Receptor protein Cytoskeletal protein Signaling protein Carrier protein Immunity related ECM protein Chaperone Cell adhesion protein Calcium binding protein Membrane traffic protein Cell junction protein Transmembrane binding protein Viral protein Surfactant Storage protein

0 5 10 15 20 25 30 35

Percentage of genes

Supplementary Figure 2 Bar graph showing classification of the five hundred downregulated genes in a given gastrointestinal primary malignancy by their function

Annals of Gastroenterology 27 Commonalities in transcriptome of GI malignancies 9

Α Β C

Large black circles: query genes grey circles: interacting or related proteins Large black circles: query genes Red: Physical interaction Large black circles: query genes Grey circles: interacting or related proteins Orange: Predicted grey circles: interacting or related proteins Purple: Co-expression Light blue: Pathway Light grey line: consolidated pathways Dark blue: colocalization Yellow: predicted pathways Functions Ochre: Shared Green: genetic interactions 1. Regulation of Ras GTPase activity Green: Genetic interaction Red: physical interaction 2. Regulation of Rho GTPase activity 3. Regulation of purine nucleotide Functions catabolic process 1. Cellular response to type I interferon 2. Response to virus 3. Regulation of nuclear division, mitosis, viral genomic replication 4. Ubiquitin ligase complex, anaphase promoting complex

D E F

Large black circles: query genes Grey circles: interacting or related proteins Large black circles: query genes Grey: Consolidated pathways Grey circles: interacting or related proteins Red: Physical interactions Grey: Consolidated pathways Orange: predicted Red: Physical interactions Light blue: Pathway Orange: Predicted Grey diamond: MirRNA targets predicted Light blue: Pathway Grey diamond: MirRNA targets predicted Functions 1. Axon guidance Functions 2. Collagen fibril organization and ECM Large black circles: query genes 1. Axon guidance component grey circles: interacting or related 2. Collagen fibril organization and ECM 3. PDGF binding proteins component 4. ER lumen Purple: Co expression 3. PDGF binding 5. Skin development 4. ER lumen Functions 6. Ras, Rho protein signal transduction 5. Skin development 1. Component of ECM 7. Epidermis, skeletal system 6. Ras, Rho protein signal transduction 2. Cell substrate adhesion development 7. Epidermis, skeletal system development 8. Regulation of cell migration 8. Regulation of cell migration 9. Cell junction assembly, cell matrix adhesion 10. Unfolded protein binding G

Large black circles: query genes Grey circles: interacting or related proteins Red: Physical interactions Orange: predicted interaction Light blue: Pathway Supplementary Figure 3 Analysis of gene networks and function using GeneMania. Light green: genetic interactions Upregulated genes that were common between three or more primary gastrointestinal Functions 1. Regulation of Mitosis, organelle fission sites were selected. The genes were then analyzed using GeneMania online tool. Analysis 2. Anaphase promotinc complex dependent ubiquiting dependent protein catabolism included automatic weighting and only the first twenty related genes were included. In each 3. Spindle fiber organization 4. Negative regulation of ubiquitin protein diagram, the large black circles represent the query genes (i.e. genes common between three ligase activity involved in mitosis or more gastrointestinal primary sites)

Annals of Gastroenterology 27 10 S. Chakraborty

Α Β C

Light grey: consolidated pathways Red: Physical interactions Functions Blue: Pathway Large black circles: query genes 1. Small molecule biosynthesis Functions Grey circles: interacting or related proteins 2. Steroid metabolism 1. GPI anchor bioassembly in ER membrane Purple: Co expression 3. Alcohol metabolism 2. C-terminal amino acid modification Light blue: Colocalization 4. Cholesterol metabolism 3. Protein lipidation Light green: genetic interactions 5. Sterol metabolism 4. Glycolipid, lipoprotein, Functions 6. Organic hydroxyl compounds, phosphatidylinositol biosynthesis 1. Negative regulation of motility carboxylic acid, organic acid and fatty 5. Glycerophospholipid metabolism 2. Androgen metabolism acid metabolism (including fatty acid 6. Fibroplast growth factor and insulin 3. Hydrolase activity beta oxidation) receptor receptor signaling pathway 7. Transferase, mannosyltransferase, phosphotransferase activity 8. Positive regulator of ERK1/ERK2 cascade

D E F

Light blue: Pathways Yellow: Predicted interaction Light grey: consolidated pathways Functions 1. Cellular response to metal ions (zinc, cadmium, inorganic metals, transition Light grey: transcription factor targets Purple: Co-expression metals) 2. Negative regulation of growth Functions 3. Primary alcohol metabolic process 1. SRP dependent contranslational protein 4. Oxidoreductase activity targeting to membrane 2. Cytosolic ribosome 3. Translation elongation and termination 4. Protein localization to ER 5. Nonsense mediated decay of mRNA 6. Viral expression, reproduction

Supplementary Figure 4 Analysis of gene networks and function using GeneMania. Downregulated genes that were common between three or more primary gastrointestinal sites were selected. The genes were then analyzed using GeneMania online tool. Analysis included automatic weighting and only the first twenty related genes were included. In each diagram, the large black circles represent the query genes (i.e. genes common between three or more gastrointestinal primary sites)

Annals of Gastroenterology 27 Commonalities in transcriptome of GI malignancies 11

Supplementary File 1 List of upregulated genes upregulated in epithelial cancers arising from the gastrointestinal tract. The numbers in row one of the excel file (i.e. 1, 2, 3 etc) correspond to the numbers in the Venn diagram shown in Fig. 1B. Thus, the genes corresponding to the number 1 (in Fig. 1B) comprise genes that are upregulated in gastric cancer and are unique to the stomach (i.e. no gene in common with those upregulated in epithelial cancers arising from one of the remaining four primary gastrointestinal sites) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 FAM72D MARCKSL1 S100P PYGO2 JUB MTERFD1 LOC100130274 INTS8 CCT6P1 HOXB7 ENAH RUVBL1 LEMD1 CDH3 TMEM9 SULF1 PTK2 SLC25A32 RIPK2 CTHRC1 LOC541471 COL4A1 IPO9 RAD21 UBE2C ADAR RCN1 C1ORF107 LOC641765 FNDC3B OCIAD2 UBQLN4 FOXQ1 FOXS1 C8ORF85 CTSA FER1L6 IGF2BP2 DAP3 PTPLAD1 MPZL1 COL11A1 GPR172A THY1 MTBP ASAP1 STK3 TAF2 YWHAZ OLFML2B MTMR11 COL5A2 FAM89A LOC100130776 RPN1 FN1 GPC3 NEBL CDH17 SCXB DUXAP10 DCAF13 SOX4 KIF14 LAPTM4B BGLAP RPL32P16 WISP1 PFDN2 PSMA7 C20ORF185 PMEPA1 AURKA PEA15 ANP32E NEK2 FLJ22536 LOC100288731 RFC4 MAGA FCRL3 KIAA1199 OSR2 SCXA UBR5 FAM83D VCAN PIGC MTHFD1L NAV1 ARNTL2 HOXA10 YEATS2 DSCC1 C20ORF199 INHBA LOC727967 LOC642502 TPX2 LOC399783 PDIA5 LYPD2 FCRL1 LOC730173 PTDSS1 SNX31 C8ORF76 DEFB115 POSTN UBD TGFB1 S100A16 CRNDE POLR2K MYBL2 NFE2L3 SFRP4 NUF2 MET TOP1P1 TIMP1 ENO2 CRTC2 LOC389137 WDR67 GDF6 RPTN DEFB116 COL3A1 ADAMTS4 IL8 PRSS38 SQLE FAM49B COX412 WFDC3 DPY19L1 S100A10 NBN MMP1 GPRC5A GBAP1 CD44 TTYH3 TGM2 C2CD4D TOP1MT PLAUR C1ORF131 DNAJC2 ETV3L WNT2 PYCRL GNA12 YTHDF1 COL1A2 RASAL2 LOC168474 PDIA4 MYOF CREB3L4 LOC647150 CST1 C20ORF118 LCE4A ATAD2 CDH11 TRAF5 SR140 OR6Y1 RUNX1 FAP DDX27 C20ORF166 ECT2 OR6P1 LOC440926 MRPL47 SFN UBAP2L LOC100132731 SLC39A4 TMEM67 LBR DPH3B LAMC2 HEATR1 HSPD1 OR10X1 ATIC IGFBP3 EIF2C2 FZD6 LCE1A TNFRSF11B FUS SLC2A1 FCRL5 EIF2S2 TATDN1 ATP6V1C1 CCT3 AHCY PLOD3 KIAA0907 TEAD4 OR10Z1 FAM60A EIF3B RAB22A VSIG8 SNAR-A1 CD276 MATN3 C1ORF182 ATP11A TNRC18 LY6E KPRP PDRG1 COL6A3 SLC26A9 BICD1 S100A6 SLC39A10 SALL4 PFDN4 LOC644504 TMEM184B GJB2 SCAMP3 XPOT NUDT1 FBXO32 PRPF3 TPD52L2 P4HA1 DENND4B HSPH1 OR10T2 LRP8 RPN2 SLCO4A1 PDP1 TRAM2 KYNU FCRL4 ENC1 C20ORF114 LRP12 BAT2L2 C20ORF123 MMP11 CHD1L SSB OR10K2 S100A2 ASXL1 S100A11 EFCAB8 TMEM2 OR2T1 NUP210L LOC727799 FAM188B TRPS1 LCE6A HMGB1L1 HDGF SLC41A1 WDYHV1 SLAMF8 PLS3 TBRG4 HEATR2 SULF2 LPCAT1 PLEC YY1AP1 ZAK EPDR1 EPPK1 SF3B4 RAE1 LOXL2 PSMB4 PAICS OR10K1 C1GALT1 FTSJ2 OSBPL3 TPX1 VOPP1 LOC100289175 HCN3 LOC100287222 SNX10 FAM83H LCE3A MAPRE1 TNFAIP6 UBE2T GRB10 OR10R2 CALU CDC25B RNF19A SLC39A14 OPN3 APOA1BP LOC728115 AEBP1 B4GALT5 LCE1C OC90 ADAM8 DTL NUP155 RXFP4 CCT6A FABP12 MRPL3 PHLDA2 MEX3A LOC441228 H2AFV GEM C1ORF204 BOP1 FSTL1 RFX5 TMEM97 VHLL TCFL5 DUSP15 FUT8 CD55 MSTO1 SNTB1 FKBP9 LRRC24 SCNM1 DLGAP4 TRIB2 CKS1B PROCR TTC24 EIF6 SLC19A1 CEP170 UBE2Q1 LOC100130289 HEY1 TMEM106B LCE2A TGIF2 TGIF1 LAMC1 FARP1 EXOC8 RAD54B EPCAM TGFB1L1 AQP10 DKC1 PCNA RAC1 LCE2C ANLN IRS1 RHOU CACYBP LOC643997 MTHFD2 GPR137B TMEM79 MMP7 PUF60 AHR LCE1F RTEL1 KPNA2 XPR1 OR2G2 MED30 ACTL6A CSTB C1ORF85 MSX2P1 CTSK FLJ43860 CENPF CPNE1 CTSE URB2 C1ORF229 LOC643837 MMP9 TMC5 C1ORF189 GART FAM92A1 ZNFX1 XKR7 EIF2AK1 STMN1 OR14A16 ITGB8 RPL39L CXCL5 GMNN KRT80 EXT1 PHF14 CKS2 MDK STX6 LOC100289405 BID CST4 GON4L C30ORF134 RP9 TTLL9 FAM177B C1ORF125 OR2W5 LRRC69 VCAM1 OR2T27 GNPAT C13ORF37 RPA3 NUDCD1 THBS2 OR2B11 FSCN1 GTF2E1 RPGRIP1L TDRD10 PPM1H PLEKHO1 DSN1 LAMB3 OR11L1 C20ORF134 BMP2 SH3KBP1 SSR2 LOC100128760 ARPC1B TNFRSF6B ISG15 OR2T8 NDUFB9 MBD4 PCDH7 IQGAP3 RBM12 ITPR3 OR2L8 POP1 IFI30 NQO1 C1ORF43 GTF2IRD1 ADRM1 AP2B1 OR2AK2 LOC100292236 HSP90B1 CSK1B PLVAP LOC728586 UCKL1 OR2L3 LAPMT4B GMPS IL13RA1 TTC13 LOC338756 C7ORF65 OR13G1 SUMO1P3 STIL NHS FAM189B AZGP1 DNTTIP1 CNIH4 C8ORF38 LRRC8D AHNAK2 SNAPIN METTL11A GGCT ACBD3 C20ORF186 NCBP2 KCNK1 SHE RBL1 FITM2 SNX27 PHF20L1 ABTB1 C16ORF75 KRTCAP2 POLR1D MTDH OR2M5 GRINA PROSAPIP1 IFI27 C1ORF104 SLC6A6 STK4 OR2M2 MMP16 APOC1 EKLF LMNA TP53RK R3HDML OR2M3 FAM183B SFXN3 PLAC8 GATAD2B LOC648152 STX16 OR2T12 HHLA1 PTPRK SLC16A3 VANGL2 RNF114 CSE1L OR2T33 SLC10A5 SPP1 WFDC2 PGLYRP3 LOC285216 TMEM189-UBE2V1 RUSC1 KLF10 UMPS amigo2 TSTD1 CD46 CEBPB TRIM11 C20ORF112 AP2M1 ANXA2P2 DUSP23 NUFUP1P KLHL38 OR6K2 C20ORF173 QTRD1 MST4 USF1 PPAT CLDN1 OR6K3 LOC341112 NOP56 SMS PVRL4 LOC729983 SNHG6 OR10J3 ZGPAT1 KIF4Q MX1 IGSF9 SNORA70 ACTR5 OR6K6 FABP9 MAGED4B HIST3H2BB PPOX LOC100132364 KIAA0406 OR6N1 KBTBD2 APP TMPRSS3 INTS3 SNHG1 C7ORF30 OR10J5 OTUD6B SERPINH1 OR14C36 C1ORF9 TRIM29 C20ORF43 OR6N2 POFUT1 MCM2 OR2T4 PCP4L1 LOC653113 PTPN12 FCRL6 FAM82B E2F3 ORT26 SMG5 LOC653877 CBX3 SLC39A1 STMN3 KDELR3 INPP4B IGSF8 LOC643856 IFT52 UBE2A C8ORF59 TMEM119 MSN ATP1A4 TRIB3 TH1L ITLN2 LRRCC1 LOC440995 CP NES NONO ADNP ILDR2 ENY2 PXDN PTTG1 ILF2 LOC119358 C7ORF40 LCE1D RPL8 COL1A1 HOXB6 LELP1 CSTF1 C7ORF44 TAGLN2 RBM38 BIN1 GSK3B ARHGAP30 CKAP2 SPINT4 HRNR IGF2BP3 PXN ZNF267 KLHDC9 LOC100271836 RRS1 S100A7L2 MAFA MCM7 MXRA5 ACSL4 XPO4 C20ORF20 RGS21 ZNF623 ATP13A3 CACNB3 NCSTN NPM1 CSPP1 TIPRL DECR1 LUM OR2T5 FDPS KIAA1549 PLEKHA8 SPRR2A LOC387820 KIAA0040 OR2G6 KIF4A XPO5 RBM39 SPRR2F NPSR1 SC65 ENDOD1 S100A7A NUPL1 C7ORF72 ISG20L2 LRRC6 TBCCD1 KIAA0101 UFC1 SLC7A1 C7ORF70 FAM58B SEPT7 APOE OXR1 USP21 IPO5 DDX56 TPR CCT6P3 ATR FAM164A C1ORF192 DIS3 TCEB1 KCNQ2 PLXND1 KIAA1217 TBCE SLC7A5 RPS21 HNRNPA2B1 SLC38A6 RBMS1 FAM20B CBFB KLHL7 SRMS ALG1L PRRG1 CENPL CCND1 SYS1 FBXO43 PLA2G7 OR14I1 SPRR2B GTBP4 UBE2V1 C20ORF135 C11ORF24 OR2T3 TOMM40L HMGB1 UNCX NPO56 GPR89B CORIN SPRR2E TAF1A TOMM34 RECQL4 MMP12 PGK1 DCST1 TNXRD3 PVT1 ZNF696 SULT1A1 MST1R SPRR2G RFC3 EXOSC4 TMEM55A GLRX PLOD2 LCE2D FABP6 GRID2IP RHPN1 PSME4 PRKCI SLAMF7 PSAT1 TMEM185B KIAA1755 SP110 SC4MOL ARHGEF11 ZC3HAV1L EIF3E GPNMB GANAB LMO4 UCK2 CDK5RAP1 TAF4 CHRAC1 GSDMD KRT19 TUG1 GARS ZFP64 SCRIB HGD MSLNL PEAR1 VEGFA PRPF6 NOD1 ECE1 PRR25 THOC2 LOC100132306 C20ORF11 PMS2L1 RAB15 MBOAT2 PRCC NOB1 ANXA9 OSGIN2 NELF TOP2A RFWD1 DCUN1D5 FIGNL1 RAPGEF5 PARP14 TCF7L2 ITLN1 ZAR1L FOXK1 VSTM2L SERPINE1 PFKP FLAD1 CDK8 MACC1 FKBP14 ACPL2 OR2M7 VPS72 LOC100289671 MRPS17 ISPD CBLB ZDHHC7 C1ORF92 MRP63 DPM1 KIAA0196 P2RX4 PI3 ASH1L TXLNG C20ORF24 LAMA5 TNIK SRD5A1 SLAMF6 N6AMT2 PHF20 LOC727848 TRIM27 LRRC8A DCST2 C13ORF29 PUS7 FAM91A1 KIF3B OR6F1 FCRLA SKA3 POLD2 ARFGAP1 TTK ORAI3 FCRLB WDR75 TRMT12 TRIB1 IFGF2BP3 CLK2 C20ORF111 C7ORF11 PANX1 KRT6B METT11B ETV4 ARFRP1 IGFBP7 RAP2B SLAMF9 DUS4L SPINLW1 NNMT EFNB2 H3F3A RBAK OGFR COL5A1 STAT1 MRPS21 B3GALT6 SPINT3 IFNGR1 F5 LMX1A LOC730107 ARHGAP39 APT6V1C1 C22ORF9 CEP350 LSM148 LOC100287081 MMP2 HK2 MAGED2 PTP14A3 LOC407835 CDR2 S100A13 SNORA43 PUS1 ID1 SEC61A1 IDS NUP133 RTKN LOC402644 LASS2 FAM110A B4GALT3 FXYD5 NFKBIL2 SH2D2A S100A4 TDRD5 LOC645139 CPNE3 NUP62 PNKD LRRC52 RHEB RBM12B RAMP3 GINS1 UHMK1 LOC646891 GPR141 SLC4A2 PPAPDC1A GBA C20ORF108 SPO11 DDX39 OAS1 SH2D1B VAPB TWISTNB AMPD2 ADSS LCE5A POLR1B UBE2W EFNA1 NOX4 DUSP12 IER4L RRM2B C19ORF21 TSC22D1 EHMT2 NUFIP1 FLJ39632 PRC1 FCGR3A ACBD6 PA2G4P4 GCNT7 LSM5 PLA2R1 C1ORF110 C20ORF177 NID2 BMS1 IL1R2 LCE1B ATP6V1F ANXA13 CHEK1 ROD1 FAM78B TGS1 NUPL2 PLAU IGFBP5 C1ORF226 TDGF3 RPL7 RARRES1 MR1 RALGPS2 NME2P1 PABPC1 PCOLCE KLF7 LOC728743 KDELC1 JPH1 lamp3 EMP2 PSMD4 RBMY2BP CRISPLD1 MSX2 LTBP2 FAM21A BZW2 DIDO1 TFRC MICAL2 TUFT1 PCID2 NKX2-4 ANGPT2 LOC728671 NCAPG SNORA60 ESF1 LRRC3 SGPP2 MRPL9 HAUS6 SPATC1 CXCL1 TCEB2 ROBO1 ABI2 STAU2 OASL AP23M2 LINGO4 B3GNTL1 FBXL6 TSPAN1 ARL4C ANGPTL1 SLC29A4 STK31 TOPBP1 SERPINB5 LHX4 LOC729513 HEATR74 PTP4A3 CASK PI4KB ACTR3B HOXA13 LEPRE1 ANKH TCHHL1 LOC389842 LOC388955 KIF22 COL6A1 RABIF LOC100288985 PL15 EFDH2 HEATR7A RGS5 GTF3A XKR9 BGN TPRG1 GABPB2 TTPAL BUB3 APOBEC3B RAPH1 IGFN1 THUMPD2 NACAD MYLK LGALS3BP TNNT2 LOC645317 RNF216 DKDELR2 LPCAT2 RCSD1 KIAA1704 BIRC7 ASPN EPH4A MAEL UTP14A HUS1 ANO1 RASA1 RPRD2 LOC348926 PRKDC PAK2 ITGA2 ZNF648 CTNNBL1 C20ORF117 ALG3 CAMPSAP1L1 VPS45 CIRH1A ZMIZ2 FYN TMCC1 SETDB1 TESC ARL4A HJURP CYP20A1 C1ORF111 PALB2 HRSP12 RAB32 SLP1 C1ORF51 SYNCRIP ZHX1 LITAF DLG1 COG2 ARMC10 GMEB2 GEMIN6 EIF4E2 C1ORF157 STAU1 ADAP1 STIP1 ASB18 GOLPH3L DUSP14 AQP1 FAM20C KAL1 HORMAD1 CLDN12 SLC7A13 KIF18B COL22A1 ANKRD45 RBM28 LOC100288015 C3ORF26 LOC200726 TEDDM1 UGGT2 SP8 TMEM176A DYTN PRUNE LOC100132832 VWDE PLOD1 NMI FAM50A TGDS MRPL13 STX1A OR4E2 FAM21C MTAP EEF1A2 LHFPL2 PSCA SMG7 UBA2 OCM PECAM1 RALA ITGA6 LOC100130109 SCAND1 POLR2H CEACAM5 TMCO1 ACFG1 LOC100288438 TJAP1 MREG TARBP1 KIAA0895 PYGB LSG1 PDXK EFNA4 GLO1 C8ORF33 rad51 IL1RAP TMEM81 RFXAP GHRHR phldb2 TMEM159 TSEN15 C7ORF68 LACTB2 slc25a44 TMSB10 TMEM183B LOC728324 FAM83A loc100129272 ZDHHC20 GLUL SNORA21 TTC35 bfaR NCK1 LCE3E GALNT6 LOC644992 arl14 LCN2 SLC9A11 EDNRA CDK13 GPR89A CRIP1 C1ORF49 NSUN5 AZIN1 JTB MLPH C1ORF220 SNHG7 GDAP1 C15 ABCC10 RGS8 PERP STK17A IFITM1 TUBA4A LIX1L TTC26 LOC646644 PRKCSH DPP3 TOR1AIP2 ZMYM2 EBAG9 RRN3P1 RUFY4 ZBTB37 pabpc1l CCDC126 PTPRG PLEKHA5 ARPC5 nkrf C7ORF71 IFI6 PTX4 BNIPL pomp ELMO2 MEST OSBPL10 POGK CBFA2T2 HSF1 TNFRSF10B C2ORF62 LYSMD1 WDR12 YKT6 ITGB4 ELF4 SNRPE ICA1 HOXA11 PFN2 SLC11A1 LCE3D TTHY3 CEP250 NOLC1 PDE4DIP THEM5 GTPBP10 HNF4A LOC440354 TIGD1 SPRR4 EXOSC8 CPVL SULT1A2 PTHLH HAX1 DACH1 DUSP10 KBTBD12 UGT1A10 RC3H1 GNL3 YWHAG DNAJB11 SLC345A4 APOBEC4 PLAGL2 LOC285359 SHC1 KRAS POLR3C CDK4 Annals of Gastroenterology 27 IMPA1 RSRC1 UGT1A5 TMOD4 DYNLRB1 HSP90AB4P DNMT3B SUMO1 GPR89C MGC11082 TOP1 SEPHS2 MYL12A OPTC PAIP1 UPP1 ACVR1 SRGAP2P1 ZNF687 UBFD1 PKD1L1 WDR72 AT1A ARL8A ABCE1 IMPAD1 DTYMK ABCA1 LGR6 C20ORF4 COL9A3 EIF5A2 HRH1 APOA2 YAP1 BHLHE23 CFB C7ORF10 PIGM XRCC2 MCM4 TRA2B SERPINE2 FCER1A DIMT1L NTSR1 GPX8 RESP18 ABL2 SCD LOC389493 PDE4A UGT1A4 ADIPOR1 DDX47 AOAH NAT9 CAPN2 C1ORF31 FAM132B ZNF716 DRAM1 CEACAM6 FLVCR1 IFITM4P C7ORF25 RNF7 C2ORF66 LRRC1 ZGPAT SHFM1 DDX60 FERMT1 NAP1L1 LOC100132418 MAPK15 C3ORF33 CEMP1 MTX1 SLC29A1 EFR3A FUBP1 TIMM17A THEM4 BRCA2 CSTL1 FAT1 N4BP1 H2AFY PMS2L3 C20ORF3 INMT BARD1 SEC16B CXCL3 NBPF16 Agr2 LDHA GOLT1A TMTC4 TIGD5 PDGFRB PRSS41 SOX13 CDC16 PARP10 SCHIP1 GREM1 CGN LOC100133317 COL28A1 MFAP2 NMU TNFAIP8L2 DARS LOC728855 TBL2 SPAG1 TROVE2 GTF21 CCNE5 HEXB OR6B2 DUSP27 SEPT14 MAFB SNRPA RIN2 C1ORD230 C13ORF23 ROMO1 TNFRSF12A PRR21 TDRKH NANP PLCG1 KLHL6 OR6B3 LCE1E LOC729375 SDR16C6 FMOD KLC1 B3GALNT2 IPO7 FAM126A SNHG10 C11ORF80 PPP1R15B USPL1 LOC100287710 FST SHCBP1 COL15A1 PHLDA1 UBE2MP1 ICAM1 HIST2H2BE XCL1 LOC5641518 CSMD3 SP140L PSME3 CAP2 SLC17A9 RALGAPB ODC1 C16ORF90 ASPM POLR3G SKAP2 DIABLO ANKRD10 OTUD7B ORC5L ETV1 FZD2 RBM44 LOC100131599 SS18L1 LRRC67 PARL SPRY4 AKR1B10 STAG3L3 TMEM64 IFI35 DYNLT3 IER5 CYP2W1 MRPS28 GLS KLHL30 INTS7 AURKAP51 SAMD12 PRKCA TERF1 FAM72A WDR74 CPXM1 ETV5 ACTR3 PBXIP1 PAFAH1B3 TRMT6 SNRPB TINK BLZF1 LOC731751 TMEM65 F2R ARPC2 HIST2H3C PABPC3 CST2 SOAT1 ACSL3 HIST2H3A EBPL UTP23 TRIO GUK1 ATP8B2 PRPS1L1 PTPRT FADS1 METTL11B HIST2H2AC IFITM2 SNORA32 DDX24 LASS6 SMYD3 OR2A5 VWC2 MINPP1 LOC342346 HIST2H2AB NSUN5P1 RUNX1T1 TM4SF18 IFI44L HMGN4 LOC389168 URGCP SEC62 SEMA3C YOD1 TROAP DBNL TANC2 DHRS9 NCF2 CBX4 PRRX1 PARP12 RASA3 SHISA4 LOC100134361 C8ORF82 NIPA2 CFLAR BCAP31 DDX18 LOC652826 LAMB1 GM2A ANZAP2 PMS2 KIF16B CDK18 FZD7 IL20 NPEPL1 ITCH ST3GAL5 CAMK2N1 OR2G3 NAA16 DEFB119 GLT25D1 COPS8 C1ORF77 DAM91A1 ZNF7 COX17 ZNF185 ZBTB41 DPEP1 GLI4 TAF1D TSTA3 PODXL KPNA7 NCOA3 FPR1 LPP KDM5B CUL4A ANKRD46 DENND3 C5ORF13 RASSF5 PNO1 IFI16 CHN2 ERO1L HNRNPU GJC3 SNRPB2 TNS3 OR10G2 LOC200030 FTSJ1 XRN2 IGHG3 RNASE13 IRF2BP2 ZNF679 BLVRA SULT1A4 SLC6A14 GTF2I DIAPH3 SPDYE1 SULT1A3 HS2ST1 LGTN MPDCD2L GGH CDC42BPA C1QTNF8 TMEM183A MANBAL ZNF704 SHOX2 ITGAM TADA1 LOC727803 GPR161 FBLIM1 TMEM189 TMEM164 SRC SNX21 HAUS7 RNASE8 COPA NSUN5P2 STARD3NL LRRC58 NCEH1 CAMSAP1L1 HSP90AB2P LOC642340 RECQLK4 YWHAB RPS6KC1 LOC100132540 LOC100286913 NUCKS1 OR5AU1 DHX9 GPSM2 PURB SPARC LYNX1 CDC73 SNORD14E EIF3H HSD17B11 OR10G3 CR1L GTF3C3 CLDN4 KIAA1804 DPY19L4 PPP2R5A CENPJ PCPL4L1 CHN1 EFNA5 FCAMR HDAC2 LOC728065 CCL18 TRADD METTL13 FAM84B LARP6 STK38L IRF6 TBC1D16 MYO1B SP100 VASH2 HCG18 NUAK1 KCNN4 PARP1 DDX21 SE1L3 LAMA3 TNFSF4 GDF15 HSPE1 IVNS1ABP TRIM67 EPHX4 MFHAS1 NRP2 C1ORF55 SLC11A2 MMP10 SPHKAP LPGAT1 SHMT2 TMEM176B LAMA4 SYT14 PRHOXNB ISY1 CCT5 TATDN3 LAGE3 HTRA1 C16ORF88 DARS2 SLC39A6 SRGN UHRF1 GGPS1 RAN CHST2 OAS2 PPPDE1 UBAC2 SET PTTG1LP NENF PSMA2 BAT1 PSMB11 C1ORF74 RPAP3 BIRC3 BOLA2B PFKFB2 TMEM206 SLC16A1 GIYD1 NME7 LOC728417 KHDRBS1 TGFB2 DDX59 FLJ41484 EFNB1 ATG16L1 GLA PHF16 ATP2C1 LIMS1 NUDT17 PSPC1 COL4A2 KRT17 EIFC2 NUP205 COL18A1 UGT1A8 FAM36A GNPDA1 COL13A1 CCNB1 EFCAB2 TUBGCP3 SCCPDH DNAJB3 C1ORF112 CHCHD2 SCRN1 UBE2I RD3 PRR7 PARVB LIME1 PDZD11 CENPI PRKC1 RAB7A C1ORDF96 ENOPH1 IGKC HOXB5 ANKRD35 OLA1 PLCH1 CA13 GORAB ZNF727 ESM1 TALDO1 SEPT8 FAM92A3 ACLY UGT1A7 LOC642587 GTF2F2 GOLIM4 HK1 MRPS14 LOC652798 LOX SSPN C1ORF53 RAD18 FOXA3 ARHGAP26 LHX9 RAP2A SSFA2 LOC340340 ARID4B BRIX1 PLSCR1 UPF3B FAM71A ZNF12 E2F1 NPL ARV1 GLS2 ACOT9 AKTIP C1ORF101 SDCCAG3 HEXA AP1S3 ABCB10 NEK5 KCNMB3 NAB1 ANGEL2 ASPH ARL6IP1 CREB1 TOMM20 PHF19 PIGX CAPG RBM34 PPIA TFAM CCL20 ANKRD34A COMT JOSD1 ITGB5 HHAT RPF2 ABHD10 ATP2A2 TRAF1P3 AP1S1 TOR3A UGT1A3 C1ORF198 PA2G4P2 CHPF GPATCH2 ORF61 LOC148145 PDFA ADAM10 DSTYK DGAT2 AGRN PM20D1 MTFR1 PFAS KCNN3 CDK6 NUP107 PIGCP1 CTPS2 SLC5A3 OR2W3 RRP1B ENPEP CRB1 UQCC C1QTNF6 C1ORF100 MPP6 MAGEF1 DCK ZC3H15 DNM1 TP53BP2 C13ORF35 MAZ WDR26 EPHB4 RAB43 DEDD HM13 PYCR1 SLC35F3 TCF4 PDZK1 HAT1 UCHL5 LOC388796 NVL SH3BP4 BRP44 ADSL RAB3GAP2 SOX12 ZNF706 C3ORF52 RIT1 TCF3 WNT3A CTSL1 WDR64 TNFAIP3 HMCN1 APBA2 HMGB2 PPFIA1 CNST SOCS3 SIPA1L2 IFITM3 SNAP47 CHERP HIST2H4B VAV2 MFSD4 MYO10 GABRE STAG1 RPS27 TRIM59 C1ORF186 DNAJC10 EDARADD C1R NBPF11 C1QC PLD5 C1ORF57 FMN2 ZNF670 TRIM58 OR1C1 C1ORF124 AHCTF1 VN1R5 ENSA OR2T29 SRGAP2 CHRM3 SDCCAG8 ZP4 OR2C3 RRP15 OR2M4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 FAM72D MARCKSL1 S100P PYGO2 JUB MTERFD1 LOC100130274 INTS8 CCT6P1 HOXB7 ENAH RUVBL1 LEMD1 CDH3 TMEM9 SULF1 PTK2 SLC25A32 RIPK2 CTHRC1 LOC541471 COL4A1 IPO9 RAD21 UBE2C ADAR RCN1 C1ORF107 LOC641765 FNDC3B OCIAD2 UBQLN4 FOXQ1 FOXS1 C8ORF85 CTSA FER1L6 IGF2BP2 DAP3 PTPLAD1 MPZL1 COL11A1 GPR172A THY1 MTBP ASAP1 STK3 TAF2 YWHAZ OLFML2B MTMR11 COL5A2 FAM89A LOC100130776 RPN1 FN1 GPC3 NEBL CDH17 SCXB DUXAP10 DCAF13 SOX4 KIF14 LAPTM4B BGLAP RPL32P16 WISP1 PFDN2 PSMA7 C20ORF185 PMEPA1 AURKA PEA15 ANP32E NEK2 FLJ22536 LOC100288731 RFC4 MAGA FCRL3 KIAA1199 OSR2 SCXA UBR5 FAM83D VCAN PIGC MTHFD1L NAV1 ARNTL2 HOXA10 YEATS2 DSCC1 C20ORF199 INHBA LOC727967 LOC642502 TPX2 LOC399783 PDIA5 LYPD2 FCRL1 LOC730173 PTDSS1 SNX31 C8ORF76 DEFB115 POSTN UBD TGFB1 S100A16 CRNDE POLR2K MYBL2 NFE2L3 SFRP4 NUF2 MET TOP1P1 TIMP1 ENO2 CRTC2 LOC389137 WDR67 GDF6 RPTN DEFB116 COL3A1 ADAMTS4 IL8 PRSS38 SQLE FAM49B COX412 WFDC3 DPY19L1 S100A10 NBN MMP1 GPRC5A GBAP1 CD44 TTYH3 TGM2 C2CD4D TOP1MT PLAUR C1ORF131 DNAJC2 ETV3L WNT2 PYCRL GNA12 YTHDF1 COL1A2 RASAL2 LOC168474 PDIA4 MYOF CREB3L4 LOC647150 CST1 C20ORF118 LCE4A ATAD2 CDH11 TRAF5 SR140 OR6Y1 RUNX1 FAP DDX27 C20ORF166 ECT2 OR6P1 LOC440926 MRPL47 SFN UBAP2L LOC100132731 SLC39A4 TMEM67 LBR DPH3B LAMC2 HEATR1 HSPD1 OR10X1 ATIC IGFBP3 EIF2C2 FZD6 LCE1A TNFRSF11B FUS SLC2A1 FCRL5 EIF2S2 TATDN1 ATP6V1C1 CCT3 AHCY PLOD3 KIAA0907 TEAD4 OR10Z1 FAM60A EIF3B RAB22A VSIG8 SNAR-A1 CD276 MATN3 C1ORF182 ATP11A TNRC18 LY6E KPRP PDRG1 COL6A3 SLC26A9 BICD1 S100A6 SLC39A10 SALL4 PFDN4 LOC644504 TMEM184B GJB2 SCAMP3 XPOT NUDT1 FBXO32 PRPF3 TPD52L2 P4HA1 DENND4B HSPH1 OR10T2 LRP8 RPN2 SLCO4A1 PDP1 TRAM2 KYNU FCRL4 ENC1 C20ORF114 LRP12 BAT2L2 C20ORF123 MMP11 CHD1L SSB OR10K2 S100A2 ASXL1 S100A11 EFCAB8 TMEM2 OR2T1 NUP210L LOC727799 FAM188B TRPS1 LCE6A HMGB1L1 HDGF SLC41A1 WDYHV1 SLAMF8 PLS3 TBRG4 HEATR2 SULF2 LPCAT1 PLEC YY1AP1 ZAK EPDR1 EPPK1 SF3B4 RAE1 LOXL2 PSMB4 PAICS OR10K1 C1GALT1 FTSJ2 OSBPL3 TPX1 VOPP1 LOC100289175 HCN3 LOC100287222 SNX10 FAM83H LCE3A MAPRE1 TNFAIP6 UBE2T GRB10 OR10R2 CALU CDC25B RNF19A SLC39A14 OPN3 APOA1BP LOC728115 AEBP1 B4GALT5 LCE1C OC90 ADAM8 DTL NUP155 RXFP4 CCT6A FABP12 MRPL3 PHLDA2 MEX3A LOC441228 H2AFV GEM C1ORF204 BOP1 FSTL1 RFX5 TMEM97 VHLL TCFL5 DUSP15 FUT8 CD55 MSTO1 SNTB1 FKBP9 LRRC24 SCNM1 DLGAP4 TRIB2 CKS1B PROCR TTC24 EIF6 SLC19A1 CEP170 UBE2Q1 LOC100130289 HEY1 TMEM106B LCE2A TGIF2 TGIF1 LAMC1 FARP1 EXOC8 RAD54B EPCAM TGFB1L1 AQP10 DKC1 PCNA RAC1 LCE2C ANLN IRS1 RHOU CACYBP LOC643997 MTHFD2 GPR137B TMEM79 MMP7 PUF60 AHR LCE1F RTEL1 KPNA2 XPR1 OR2G2 MED30 ACTL6A CSTB C1ORF85 MSX2P1 CTSK FLJ43860 CENPF CPNE1 CTSE URB2 C1ORF229 LOC643837 MMP9 TMC5 C1ORF189 GART FAM92A1 ZNFX1 XKR7 EIF2AK1 STMN1 OR14A16 ITGB8 RPL39L CXCL5 GMNN KRT80 EXT1 PHF14 CKS2 MDK STX6 LOC100289405 BID CST4 GON4L C30ORF134 RP9 TTLL9 FAM177B C1ORF125 OR2W5 LRRC69 VCAM1 OR2T27 GNPAT C13ORF37 RPA3 NUDCD1 THBS2 OR2B11 FSCN1 GTF2E1 RPGRIP1L TDRD10 PPM1H PLEKHO1 DSN1 LAMB3 OR11L1 C20ORF134 BMP2 SH3KBP1 SSR2 LOC100128760 ARPC1B TNFRSF6B ISG15 OR2T8 NDUFB9 MBD4 PCDH7 IQGAP3 MYC RBM12 ITPR3 OR2L8 POP1 IFI30 NQO1 C1ORF43 GTF2IRD1 ADRM1 AP2B1 OR2AK2 LOC100292236 HSP90B1 CSK1B PLVAP LOC728586 UCKL1 OR2L3 LAPMT4B GMPS IL13RA1 TTC13 LOC338756 C7ORF65 OR13G1 SUMO1P3 STIL NHS FAM189B AZGP1 DNTTIP1 CNIH4 C8ORF38 LRRC8D AHNAK2 SNAPIN METTL11A GGCT ACBD3 C20ORF186 NCBP2 KCNK1 SHE RBL1 FITM2 SNX27 PHF20L1 ABTB1 C16ORF75 KRTCAP2 POLR1D MTDH OR2M5 GRINA PROSAPIP1 IFI27 C1ORF104 SLC6A6 STK4 OR2M2 MMP16 APOC1 EKLF LMNA TP53RK R3HDML OR2M3 FAM183B SFXN3 PLAC8 GATAD2B LOC648152 STX16 OR2T12 HHLA1 PTPRK SLC16A3 VANGL2 RNF114 CSE1L OR2T33 SLC10A5 SPP1 WFDC2 PGLYRP3 LOC285216 TMEM189-UBE2V1 RUSC1 KLF10 UMPS amigo2 TSTD1 CD46 CEBPB TRIM11 C20ORF112 AP2M1 ANXA2P2 DUSP23 NUFUP1P KLHL38 OR6K2 C20ORF173 QTRD1 MST4 USF1 PPAT CLDN1 OR6K3 LOC341112 NOP56 SMS PVRL4 LOC729983 SNHG6 OR10J3 ZGPAT1 KIF4Q MX1 IGSF9 SNORA70 ACTR5 OR6K6 FABP9 MAGED4B HIST3H2BB PPOX LOC100132364 KIAA0406 OR6N1 KBTBD2 APP TMPRSS3 INTS3 SNHG1 C7ORF30 OR10J5 OTUD6B SERPINH1 OR14C36 C1ORF9 TRIM29 C20ORF43 OR6N2 POFUT1 MCM2 OR2T4 PCP4L1 LOC653113 PTPN12 FCRL6 FAM82B E2F3 ORT26 SMG5 LOC653877 CBX3 SLC39A1 STMN3 KDELR3 INPP4B IGSF8 LOC643856 IFT52 UBE2A C8ORF59 TMEM119 MSN ATP1A4 TRIB3 TH1L ITLN2 LRRCC1 LOC440995 CP NES NONO ADNP ILDR2 ENY2 PXDN PTTG1 ILF2 LOC119358 C7ORF40 LCE1D RPL8 COL1A1 HOXB6 LELP1 CSTF1 C7ORF44 TAGLN2 RBM38 BIN1 GSK3B ARHGAP30 CKAP2 SPINT4 HRNR IGF2BP3 PXN ZNF267 KLHDC9 LOC100271836 RRS1 S100A7L2 MAFA MCM7 MXRA5 ACSL4 XPO4 C20ORF20 RGS21 ZNF623 ATP13A3 CACNB3 NCSTN NPM1 CSPP1 TIPRL DECR1 LUM OR2T5 FDPS KIAA1549 PLEKHA8 SPRR2A LOC387820 KIAA0040 OR2G6 KIF4A XPO5 RBM39 SPRR2F NPSR1 SC65 ENDOD1 S100A7A NUPL1 C7ORF72 ISG20L2 LRRC6 TBCCD1 KIAA0101 UFC1 SLC7A1 C7ORF70 FAM58B SEPT7 APOE OXR1 USP21 IPO5 DDX56 TPR CCT6P3 ATR FAM164A C1ORF192 DIS3 TCEB1 KCNQ2 PLXND1 KIAA1217 TBCE SLC7A5 RPS21 HNRNPA2B1 SLC38A6 RBMS1 FAM20B CBFB KLHL7 SRMS ALG1L PRRG1 CENPL CCND1 SYS1 FBXO43 PLA2G7 OR14I1 SPRR2B GTBP4 UBE2V1 C20ORF135 C11ORF24 OR2T3 TOMM40L HMGB1 UNCX NPO56 GPR89B CORIN SPRR2E TAF1A TOMM34 RECQL4 MMP12 PGK1 DCST1 TNXRD3 PVT1 ZNF696 SULT1A1 MST1R SPRR2G RFC3 EXOSC4 TMEM55A GLRX PLOD2 LCE2D FABP6 GRID2IP RHPN1 PSME4 PRKCI SLAMF7 PSAT1 TMEM185B KIAA1755 SP110 SC4MOL ARHGEF11 ZC3HAV1L EIF3E GPNMB GANAB LMO4 UCK2 CDK5RAP1 TAF4 CHRAC1 GSDMD KRT19 TUG1 GARS ZFP64 SCRIB HGD MSLNL PEAR1 VEGFA PRPF6 NOD1 ECE1 PRR25 THOC2 LOC100132306 C20ORF11 PMS2L1 RAB15 MBOAT2 PRCC NOB1 ANXA9 OSGIN2 NELF TOP2A RFWD1 DCUN1D5 FIGNL1 RAPGEF5 PARP14 TCF7L2 ITLN1 ZAR1L FOXK1 VSTM2L SERPINE1 PFKP FLAD1 CDK8 MACC1 FKBP14 ACPL2 OR2M7 VPS72 LOC100289671 MRPS17 ISPD CBLB ZDHHC7 C1ORF92 MRP63 DPM1 KIAA0196 P2RX4 PI3 ASH1L TXLNG C20ORF24 LAMA5 TNIK SRD5A1 SLAMF6 N6AMT2 PHF20 LOC727848 TRIM27 LRRC8A DCST2 C13ORF29 PUS7 FAM91A1 KIF3B OR6F1 FCRLA SKA3 POLD2 ARFGAP1 TTK ORAI3 FCRLB WDR75 TRMT12 TRIB1 IFGF2BP3 CLK2 C20ORF111 C7ORF11 PANX1 KRT6B METT11B ETV4 ARFRP1 IGFBP7 RAP2B SLAMF9 DUS4L SPINLW1 NNMT EFNB2 H3F3A RBAK OGFR COL5A1 STAT1 MRPS21 B3GALT6 SPINT3 IFNGR1 F5 LMX1A LOC730107 ARHGAP39 APT6V1C1 C22ORF9 CEP350 LSM148 LOC100287081 MMP2 HK2 MAGED2 PTP14A3 LOC407835 CDR2 S100A13 SNORA43 PUS1 ID1 SEC61A1 IDS NUP133 RTKN LOC402644 LASS2 FAM110A B4GALT3 FXYD5 NFKBIL2 SH2D2A S100A4 TDRD5 LOC645139 CPNE3 NUP62 PNKD LRRC52 RHEB RBM12B RAMP3 GINS1 UHMK1 LOC646891 GPR141 SLC4A2 PPAPDC1A GBA C20ORF108 SPO11 DDX39 OAS1 SH2D1B VAPB TWISTNB AMPD2 ADSS LCE5A POLR1B UBE2W EFNA1 NOX4 DUSP12 IER4L RRM2B C19ORF21 TSC22D1 EHMT2 NUFIP1 FLJ39632 PRC1 FCGR3A ACBD6 PA2G4P4 GCNT7 LSM5 PLA2R1 C1ORF110 C20ORF177 NID2 BMS1 IL1R2 LCE1B ATP6V1F ANXA13 CHEK1 ROD1 FAM78B TGS1 NUPL2 PLAU IGFBP5 C1ORF226 TDGF3 RPL7 RARRES1 MR1 RALGPS2 NME2P1 PABPC1 PCOLCE KLF7 LOC728743 KDELC1 JPH1 lamp3 EMP2 PSMD4 RBMY2BP CRISPLD1 MSX2 LTBP2 FAM21A BZW2 DIDO1 TFRC MICAL2 TUFT1 PCID2 NKX2-4 ANGPT2 LOC728671 NCAPG SNORA60 ESF1 LRRC3 SGPP2 MRPL9 HAUS6 SPATC1 CXCL1 TCEB2 ROBO1 ABI2 STAU2 OASL AP23M2 LINGO4 B3GNTL1 FBXL6 TSPAN1 ARL4C ANGPTL1 SLC29A4 STK31 TOPBP1 SERPINB5 LHX4 LOC729513 HEATR74 PTP4A3 CASK PI4KB ACTR3B HOXA13 LEPRE1 ANKH TCHHL1 LOC389842 LOC388955 KIF22 COL6A1 RABIF LOC100288985 PL15 EFDH2 HEATR7A RGS5 GTF3A XKR9 BGN TPRG1 GABPB2 TTPAL BUB3 APOBEC3B RAPH1 IGFN1 THUMPD2 NACAD MYLK LGALS3BP TNNT2 LOC645317 RNF216 DKDELR2 LPCAT2 RCSD1 KIAA1704 BIRC7 ASPN EPH4A MAEL UTP14A HUS1 ANO1 RASA1 RPRD2 LOC348926 PRKDC PAK2 ITGA2 ZNF648 CTNNBL1 C20ORF117 ALG3 CAMPSAP1L1 VPS45 CIRH1A ZMIZ2 FYN TMCC1 SETDB1 TESC ARL4A HJURP CYP20A1 C1ORF111 PALB2 HRSP12 RAB32 SLP1 C1ORF51 SYNCRIP ZHX1 LITAF DLG1 COG2 ARMC10 GMEB2 GEMIN6 EIF4E2 C1ORF157 STAU1 ADAP1 STIP1 ASB18 GOLPH3L DUSP14 AQP1 FAM20C KAL1 HORMAD1 CLDN12 SLC7A13 KIF18B COL22A1 ANKRD45 RBM28 LOC100288015 C3ORF26 LOC200726 TEDDM1 UGGT2 SP8 TMEM176A DYTN PRUNE LOC100132832 VWDE PLOD1 NMI FAM50A TGDS MRPL13 STX1A OR4E2 FAM21C MTAP EEF1A2 LHFPL2 PSCA SMG7 UBA2 OCM PECAM1 RALA ITGA6 LOC100130109 SCAND1 POLR2H CEACAM5 TMCO1 ACFG1 LOC100288438 TJAP1 MREG TARBP1 KIAA0895 PYGB LSG1 PDXK EFNA4 GLO1 C8ORF33 rad51 IL1RAP TMEM81 RFXAP GHRHR phldb2 TMEM159 TSEN15 C7ORF68 LACTB2 slc25a44 TMSB10 TMEM183B LOC728324 FAM83A loc100129272 ZDHHC20 GLUL SNORA21 TTC35 bfaR NCK1 LCE3E GALNT6 LOC644992 arl14 LCN2 SLC9A11 EDNRA CDK13 GPR89A CRIP1 C1ORF49 NSUN5 AZIN1 JTB MLPH C1ORF220 SNHG7 GDAP1 C15 ABCC10 RGS8 PERP STK17A IFITM1 TUBA4A LIX1L TTC26 12LOC646644 S.PRKCSH ChakrabortyDPP3 TOR1AIP2 ZMYM2 EBAG9 RRN3P1 RUFY4 ZBTB37 pabpc1l CCDC126 PTPRG PLEKHA5 ARPC5 nkrf C7ORF71 IFI6 PTX4 BNIPL pomp ELMO2 MEST OSBPL10 POGK CBFA2T2 HSF1 TNFRSF10B C2ORF62 LYSMD1 WDR12 YKT6 ITGB4 ELF4 SNRPE ICA1 HOXA11 PFN2 SLC11A1 LCE3D TTHY3 SupplementaryCEP250 NOLC1 FilePDE4DIP 1 (continued)THEM5 GTPBP10 HNF4A LOC440354 TIGD1 SPRR4 EXOSC8 CPVL SULT1A2 PTHLH HAX1 DACH1 DUSP10 KBTBD12 UGT1A10 RC3H1 GNL3 YWHAG DNAJB11 SLC345A4 APOBEC4 PLAGL2 LOC285359 SHC1 KRAS POLR3C CDK4 IMPA1 RSRC1 UGT1A5 TMOD4 DYNLRB1 HSP90AB4P DNMT3B SUMO1 GPR89C MGC11082 TOP1 SEPHS2 MYL12A OPTC PAIP1 UPP1 ACVR1 SRGAP2P1 ZNF687 UBFD1 PKD1L1 WDR72 AT1A ARL8A ABCE1 IMPAD1 DTYMK ABCA1 LGR6 C20ORF4 COL9A3 EIF5A2 HRH1 APOA2 YAP1 BHLHE23 CFB C7ORF10 PIGM XRCC2 MCM4 TRA2B SERPINE2 FCER1A DIMT1L NTSR1 GPX8 RESP18 ABL2 SCD LOC389493 PDE4A UGT1A4 ADIPOR1 DDX47 AOAH NAT9 CAPN2 C1ORF31 FAM132B ZNF716 DRAM1 CEACAM6 FLVCR1 IFITM4P C7ORF25 RNF7 C2ORF66 LRRC1 ZGPAT SHFM1 DDX60 FERMT1 NAP1L1 LOC100132418 MAPK15 C3ORF33 CEMP1 MTX1 SLC29A1 EFR3A FUBP1 TIMM17A THEM4 BRCA2 CSTL1 FAT1 N4BP1 H2AFY PMS2L3 C20ORF3 INMT BARD1 SEC16B CXCL3 NBPF16 Agr2 LDHA GOLT1A TMTC4 TIGD5 PDGFRB PRSS41 SOX13 CDC16 PARP10 SCHIP1 GREM1 CGN LOC100133317 COL28A1 MFAP2 NMU TNFAIP8L2 DARS LOC728855 TBL2 SPAG1 TROVE2 GTF21 CCNE5 HEXB OR6B2 DUSP27 SEPT14 MAFB SNRPA RIN2 C1ORD230 C13ORF23 ROMO1 TNFRSF12A PRR21 TDRKH NANP PLCG1 KLHL6 OR6B3 LCE1E LOC729375 SDR16C6 FMOD KLC1 B3GALNT2 IPO7 FAM126A SNHG10 C11ORF80 PPP1R15B USPL1 LOC100287710 FST SHCBP1 COL15A1 PHLDA1 UBE2MP1 ICAM1 HIST2H2BE XCL1 LOC5641518 CSMD3 SP140L PSME3 CAP2 SLC17A9 RALGAPB ODC1 C16ORF90 ASPM POLR3G SKAP2 DIABLO ANKRD10 OTUD7B ORC5L ETV1 FZD2 RBM44 LOC100131599 SS18L1 LRRC67 PARL SPRY4 AKR1B10 STAG3L3 TMEM64 IFI35 DYNLT3 IER5 CYP2W1 MRPS28 GLS KLHL30 INTS7 AURKAP51 SAMD12 PRKCA TERF1 FAM72A WDR74 CPXM1 ETV5 ACTR3 PBXIP1 PAFAH1B3 TRMT6 SNRPB TINK BLZF1 LOC731751 TMEM65 F2R ARPC2 HIST2H3C PABPC3 CST2 SOAT1 ACSL3 HIST2H3A EBPL UTP23 TRIO GUK1 ATP8B2 PRPS1L1 PTPRT FADS1 METTL11B HIST2H2AC IFITM2 SNORA32 DDX24 LASS6 SMYD3 OR2A5 VWC2 MINPP1 LOC342346 HIST2H2AB NSUN5P1 RUNX1T1 TM4SF18 IFI44L HMGN4 LOC389168 URGCP SEC62 SEMA3C YOD1 TROAP DBNL TANC2 DHRS9 NCF2 CBX4 PRRX1 PARP12 RASA3 SHISA4 LOC100134361 C8ORF82 NIPA2 CFLAR BCAP31 DDX18 LOC652826 LAMB1 GM2A ANZAP2 PMS2 KIF16B CDK18 FZD7 IL20 NPEPL1 ITCH ST3GAL5 CAMK2N1 OR2G3 NAA16 DEFB119 GLT25D1 COPS8 C1ORF77 DAM91A1 ZNF7 COX17 ZNF185 ZBTB41 DPEP1 GLI4 TAF1D TSTA3 PODXL KPNA7 NCOA3 FPR1 LPP KDM5B CUL4A ANKRD46 DENND3 C5ORF13 RASSF5 PNO1 IFI16 CHN2 ERO1L HNRNPU GJC3 SNRPB2 TNS3 OR10G2 LOC200030 FTSJ1 XRN2 IGHG3 RNASE13 IRF2BP2 ZNF679 BLVRA SULT1A4 SLC6A14 GTF2I DIAPH3 SPDYE1 SULT1A3 HS2ST1 LGTN MPDCD2L GGH CDC42BPA C1QTNF8 TMEM183A MANBAL ZNF704 SHOX2 ITGAM TADA1 LOC727803 GPR161 FBLIM1 TMEM189 TMEM164 SRC SNX21 HAUS7 RNASE8 COPA NSUN5P2 STARD3NL LRRC58 NCEH1 CAMSAP1L1 HSP90AB2P LOC642340 RECQLK4 YWHAB RPS6KC1 LOC100132540 LOC100286913 NUCKS1 OR5AU1 DHX9 GPSM2 PURB SPARC LYNX1 CDC73 SNORD14E EIF3H HSD17B11 OR10G3 CR1L GTF3C3 CLDN4 KIAA1804 DPY19L4 PPP2R5A CENPJ PCPL4L1 CHN1 EFNA5 FCAMR HDAC2 LOC728065 CCL18 TRADD METTL13 FAM84B LARP6 STK38L IRF6 TBC1D16 MYO1B SP100 VASH2 HCG18 NUAK1 KCNN4 PARP1 DDX21 SE1L3 LAMA3 TNFSF4 GDF15 HSPE1 IVNS1ABP TRIM67 EPHX4 MFHAS1 NRP2 C1ORF55 SLC11A2 MMP10 SPHKAP LPGAT1 SHMT2 TMEM176B LAMA4 SYT14 PRHOXNB ISY1 CCT5 TATDN3 LAGE3 HTRA1 C16ORF88 DARS2 SLC39A6 SRGN UHRF1 GGPS1 RAN CHST2 OAS2 PPPDE1 UBAC2 SET PTTG1LP NENF PSMA2 BAT1 PSMB11 C1ORF74 RPAP3 BIRC3 BOLA2B PFKFB2 TMEM206 SLC16A1 GIYD1 NME7 LOC728417 KHDRBS1 TGFB2 DDX59 FLJ41484 EFNB1 ATG16L1 GLA PHF16 ATP2C1 LIMS1 NUDT17 PSPC1 COL4A2 KRT17 EIFC2 NUP205 COL18A1 UGT1A8 FAM36A GNPDA1 COL13A1 CCNB1 EFCAB2 TUBGCP3 SCCPDH DNAJB3 C1ORF112 CHCHD2 SCRN1 UBE2I RD3 PRR7 PARVB LIME1 PDZD11 CENPI PRKC1 RAB7A C1ORDF96 ENOPH1 IGKC HOXB5 ANKRD35 OLA1 PLCH1 CA13 GORAB ZNF727 ESM1 TALDO1 SEPT8 FAM92A3 ACLY UGT1A7 LOC642587 GTF2F2 GOLIM4 HK1 MRPS14 LOC652798 LOX SSPN C1ORF53 RAD18 FOXA3 ARHGAP26 LHX9 RAP2A SSFA2 LOC340340 ARID4B BRIX1 PLSCR1 UPF3B FAM71A ZNF12 E2F1 NPL ARV1 GLS2 ACOT9 AKTIP C1ORF101 SDCCAG3 HEXA AP1S3 ABCB10 NEK5 KCNMB3 NAB1 ANGEL2 ASPH ARL6IP1 CREB1 TOMM20 PHF19 PIGX CAPG RBM34 PPIA TFAM CCL20 ANKRD34A COMT JOSD1 ITGB5 HHAT RPF2 ABHD10 ATP2A2 TRAF1P3 AP1S1 TOR3A UGT1A3 C1ORF198 PA2G4P2 CHPF GPATCH2 ORF61 LOC148145 PDFA ADAM10 DSTYK DGAT2 AGRN PM20D1 MTFR1 PFAS KCNN3 CDK6 NUP107 PIGCP1 CTPS2 SLC5A3 OR2W3 RRP1B ENPEP CRB1 UQCC C1QTNF6 C1ORF100 MPP6 MAGEF1 DCK ZC3H15 DNM1 TP53BP2 C13ORF35 MAZ WDR26 EPHB4 RAB43 DEDD HM13 PYCR1 SLC35F3 TCF4 PDZK1 HAT1 UCHL5 LOC388796 NVL SH3BP4 BRP44 ADSL RAB3GAP2 SOX12 ZNF706 C3ORF52 RIT1 TCF3 WNT3A CTSL1 WDR64 TNFAIP3 HMCN1 APBA2 HMGB2 PPFIA1 CNST SOCS3 SIPA1L2 IFITM3 SNAP47 CHERP HIST2H4B VAV2 MFSD4 MYO10 GABRE STAG1 RPS27 TRIM59 C1ORF186 DNAJC10 EDARADD C1R NBPF11 C1QC PLD5 C1ORF57 FMN2 ZNF670 TRIM58 OR1C1 C1ORF124 AHCTF1 VN1R5 ENSA OR2T29 SRGAP2 CHRM3 SDCCAG8 ZP4 OR2C3 RRP15 OR2M4

Annals of Gastroenterology 27 Commonalities in transcriptome of GI malignancies 13

Supplementary File 2 List of downregulated genes downregulated in epithelial cancers arising from the gastrointestinal tract. The numbers in row one of the excel file (i.e. 1, 2, 3 etc) correspond to the numbers in the Venn diagram shown in Fig. 2B. Thus, the genes corresponding to the number 1 (in Fig. 2B) comprise genes that are downregulated in gastric cancer and are unique to the stomach (i.e. no gene in common with those downregulated in epithelial cancers arising from one of the remaining four primary gastrointestinal sites) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 C2ORF88 CWH43 FLJ42875 AGXT2L1 FLJ11235 KLK13 ECM1 KAT2B RTN4RL1 NR5A2 NAT2 NCRNA00081 UBE2D3 SNX24 NEDD4L ADH1A ETFDH NAAA LOC728392 PAIP2B PDCD4 TMEM220 INCA1 DHRS11 IL2 LOC100131825 CLDN22 HPGD KANK1 PDLIM2 GPD1L OR1D5 P2RX1 KBTBD11 LOC100287917 RBM47 HMSD ADH1B CHP AMAC1L3 PMS2L11 ACADVL ACAT1 LOC340888 D4S234E KRTAP10-2 CCDC110 LOC389369 SYNGR1 EXPH5 PINK1 OVCA2 SLC4A4 NAT1 KLB TCEB3CL AGPAT9 GGT6 RNF222 EPHX2 TSPAN7 KIAA1109 LOC145837 HELT RELL1 GPX3 BBOX1 TP53I3 CNKSR3 SNRPN C17ORF87 SSBP2 ATP2A3 ADH1C SHISA6 ZZEF1 TP53INP2 ELL2 PER1 FRG2 FAM107A ZDHHC21 C4ORF3 SCNN1B ENPP1 CBLN2 ACADS PIGN TOM1L2 HADH SLC16A13 RILP C14ORF139 EPB41L4A ATP1B2 FAM149A LPHN3 HIST1H2AC ARHGAP10 NDRG2 ODF4 ME2 LIFR ATP9B CAMK2D SPDYE4 GPS2 UGT1A HOPX FAM69C MMRN1 GCNT2 RGS12 KAZ AHNAK TRMT11 WSCD1 MT2A BCL2 MT1G CYP4V2 SEMA6D FBXO8 SEC11C NDST3 IQGAP2 RPL29P5 ALDH4A1 EPB41L3 RPH3AL ANPEP MT1H RNF152 PLAC8 C17ORF107 WDR7 UBE2G1 SUGT1L1 TMSL3 CLRN2 ALDH3A2 PLEKHN1 CPEB3 SPNS3 MBP MT1X ZFP3 MT1F KCTD11 CCDC68 RDH12 GLTPD2 HSD17B13 STOX2 DSG1 AQP3 HIGD1A CLU PDK4 ZG16 ATP5A1 PIRT C17ORF61 LOC401022 SPINK7 CBS QRFPR SPINK2 FNDC4 ASAP3 C8ORF42 KLF9 CAMTA2 NTN1 BRP44L RPL26 SULT1A2 TMEM154 C3ORF47 IGKC ABCG2 AMFR GLTP KLKB1 LOC283070 HES3 IGL@ TRPV3 C1ORF115 UBL3 TNFSF12-TNFSF13 FGA LOC100287069 ABAT CES2 NLGN2 MBD1 C7 ASPA PLCL2 SPINK8 KRTAP10-6 LOC400960 MT1P2 ADK MALL C6 CA4 C17ORF76 C17ORF91 DSC2 GPT2 SGK1 FAM13A UNC5C RND3 EIF4E3 AOX1 C17ORF59 NCOR1 MT1E LOC283267 C20ORF56 C4ORF37 MT1L PTH1R KIF4CP CLN8 TEX11 LDHD PITPNM3 FAM82A1 AMT NHEDC1 KCNIP4 VPS4B MFSD6L SMAD4 HSD17B2 C21ORF33 LRRC30 CYB5A MAPK10 C4ORF34 SMPD1 CENPV TNXB TMEM88B MT1M LOC389033 VPS53 SLC10A6 HAPLN1 RIOK3 TMEM95 SEL1L PPP2CB MAP2K4 KIAA0125 KRTAP19-8 DHRS7C DDX60 CLTB CYB5D1 IGHA1 SCARA5 NR3C2 SULTIA1 KRTAP20-3 LOC285501 SULT1B1 STIM1 ARID1B MAOA ATP8B1 SOX15 CYB5D2 RAB27A GAB1 PLG CA2 PTP4A1 KRTAP10-9 EP400NL TNFRSF13B SQRDL SLC16A11 GBA3 PLD6 NAP1L5 SLC9A1 MAPK7 SLC39A8 SPPL2A LOC100128977 GPM6A RICH2 SECISBP2L ESR1 PLCE1 SGSM2 MST1P9 FLJ32063 PTPN21 TRPM6 ZNF286B LRIT3 HPGDS PQLC1 CHGA EVPLL HYAL1 UGDH LOC100287411 C4ORF32 PPARGC1A UGT2A3 CDRT15 TBC1D9 FUCA1 WWC2 CLEC3B ABCA8 MPDU1 LOC285878 MIER3 C17ORF74 PKIB CHL1 ADH6 ENTPD5 SETBP1 BDH2 FLJ40330 PPAP2A ACSL1 SMCHD1 TMEM88 OSBPL1A TRPV1 DHDDS SYNPO2 ZNF575 ODZ3 ACAA2 ANXA10 KIAA1211 ADH4 SMPDL3A CLEC10A ABHD3 PLA2G12A PCK1 ZSWIM7 TNFRSF11A MTTP LOC100128573 SEC24B ANKRD12 LOC100288798 ANK3 ING2 SLC30A10 AFF1 METTL7A MYOCD RUNDC3B SLC25A35 LAMA1 CXCL14 ITM2C CAMKK1 SRI DNAH9 SEMA6A HERPUD1 KIAA1468 HERC5 PPP2R3A SHPK C11ORF86 ZNF18 LPAR1 VAPA RDH5 CALM1 SYTL4 CYTL4 CNTN3 SLC17A4 AQP8 CPM FECH KLF4 LOC646627 PAG1 CYTSB MT1JP UGP2 LOC100129069 CLDN23 CA7 CHP2 SLC26A2 PAPSS2 CDKN2B LOC285758 LOC100289632 IGLV2-14 RETSAT CDH19 NKX2-3 MOBKL2B ZNF24 MOGAT2 LOC100133944 PAQR5 FTHL20 TRANK1 SOCS6 SLC25A34 LOC642513 HDHD2 ZADH2 LOC284112 RNF125 FAM59A CLDN8 AKR1B10 LOC728003 LOC100133337 CNNM4 MPPE1 IL17REL KCNK10 TTLL8 PPARGC1B PLAC2 AP3S2 PRKCB LOC100289019 TNXA TMEM37 DPF3 FXYD1 ENDOD1 FBLIM1 WDR78 CD36 FAM162A ANO5 UQCR10 CES3 LOC283435 ASXL3 ANF397OS GNA11 SLC41A2 LOC346329 AHCYL2 HHLA2 LOC653506 MMP28 LOC100132938 BTNL3 PTPRH VIPR SECTM1 SLC2A3P1 CASP7 APC LOC641367 FAM126B SLC2A13 FLJ30901 NHSL1 NR3C1 LOC729468 KIF16B TRGC2 PDE8A PYY2 LOC100128823 ARSA GDPD3 CA12 TSHZ1 HOXD1 CAPN2 C5ORF30 ADD1 CNNM2 Annals of Gastroenterology 27 TLCD2 TRGV9 TNFRSF17 ZBTB7C HSPC159 OAF LOC100131506 MPND CHMP2 TTC38 BMP5 C1ORF201 C4ORF19 LOC100131014 ANGPTL7 APPL2 ZFYVE28 MFN2 PTGDR FAM5C PACSIN2 CFD VSIG CD177 ACO2 MARCH8 ADCY9 RNF138 CLMN TMEM100 C10ORF54 MRPL35 MBOAT1 LOC727916 CETN4P FAM150B PAFAH2 CLDN7 OSTBETA BEST2 LOC100133075 GOLM1 TSPAN3 ABCA5 TMCC3 FAM30A TEF CP NOVA1 AB13BP FNIP2 TL3 PRAMEF20 USP2 PRAMEF21 CALCOCO2 SLCO2A1 MTUS1 MIER1 MS4A12 FLVCR2 AFG3L2 KCNMA1 PRKACB PAFAH1B1 NCRNA00207 UGT1A8 TMEM82 CDKL1 FAM107B KCTD9 CPNE8 HSBP1L1 BCAR3 TST PYY DISP2 LRRC66 KCTD1 PRIMA1 KIAA0513 MTHFR SELENBP1 PRAMEF22 SFTA1P LRRC1 PRAMEF5 HSD11B2 PADI2 P2RY14 PRAMEF15 PRAMEF9 KLF13 PRAMEF13 TMEM30B PRAMEF14 FLJ227763 GCG CDC42SE2 LPCAT4 HADHA STON2 C16ORF62 IL6R LOC440563 PGM1 PPM1A PGPEP1 CTDP1 AGXT2L2 CTSG SLC25A23 LETM1 MUL1 GAK EDN3 GRAMD3 SFRP1 HEXIM1 C15ORF53 FTHL2 TRD@ SESN2 ATP13A4 POLD4 PDE5A SNAP29 LUZP1 HPSE TUBAL3 STMN2 ATG4D PLXNA2 FGFR2 STYK1 LOC391769 C18ORF32 NCF1B FMO4 MYO15B HMGCL C18ORF18 VPS13D MNMAT1 CDC14A FAM189A1 MEP1B TNFSF12-TNFS13 CTNND1 PADI6 DMXL1 RAB37 MEI1 RPS6KA1 SMG6 GIMAP1 CEACAM1 CDHR5 PLS1 PDCD6IP GCOM1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 C2ORF88 CWH43 FLJ42875 AGXT2L1 FLJ11235 KLK13 ECM1 KAT2B RTN4RL1 NR5A2 NAT2 NCRNA00081 UBE2D3 SNX24 NEDD4L ADH1A ETFDH NAAA LOC728392 PAIP2B PDCD4 TMEM220 INCA1 DHRS11 IL2 LOC100131825 CLDN22 HPGD KANK1 PDLIM2 GPD1L OR1D5 P2RX1 KBTBD11 LOC100287917 RBM47 HMSD ADH1B CHP AMAC1L3 PMS2L11 ACADVL ACAT1 LOC340888 D4S234E KRTAP10-2 CCDC110 LOC389369 SYNGR1 EXPH5 PINK1 OVCA2 SLC4A4 NAT1 KLB TCEB3CL AGPAT9 GGT6 RNF222 EPHX2 TSPAN7 KIAA1109 LOC145837 HELT RELL1 GPX3 BBOX1 TP53I3 CNKSR3 SNRPN C17ORF87 SSBP2 ATP2A3 ADH1C SHISA6 ZZEF1 TP53INP2 ELL2 PER1 FRG2 FAM107A ZDHHC21 C4ORF3 SCNN1B ENPP1 CBLN2 ACADS PIGN TOM1L2 HADH SLC16A13 RILP C14ORF139 EPB41L4A ATP1B2 FAM149A LPHN3 HIST1H2AC ARHGAP10 NDRG2 ODF4 ME2 LIFR ATP9B CAMK2D SPDYE4 GPS2 UGT1A HOPX FAM69C MMRN1 GCNT2 RGS12 KAZ AHNAK TRMT11 WSCD1 MT2A BCL2 MT1G CYP4V2 SEMA6D FBXO8 SEC11C NDST3 IQGAP2 RPL29P5 ALDH4A1 EPB41L3 RPH3AL ANPEP MT1H RNF152 PLAC8 C17ORF107 WDR7 UBE2G1 SUGT1L1 TMSL3 CLRN2 ALDH3A2 PLEKHN1 CPEB3 SPNS3 MBP MT1X ZFP3 MT1F KCTD11 CCDC68 RDH12 GLTPD2 HSD17B13 STOX2 DSG1 AQP3 HIGD1A CLU PDK4 ZG16 ATP5A1 PIRT C17ORF61 LOC401022 SPINK7 CBS QRFPR SPINK2 FNDC4 ASAP3 C8ORF42 KLF9 CAMTA2 NTN1 BRP44L RPL26 SULT1A2 TMEM154 C3ORF47 IGKC ABCG2 AMFR GLTP KLKB1 LOC283070 HES3 IGL@ TRPV3 C1ORF115 UBL3 TNFSF12-TNFSF13 FGA LOC100287069 ABAT CES2 NLGN2 MBD1 C7 ASPA PLCL2 SPINK8 KRTAP10-6 LOC400960 MT1P2 ADK MALL C6 CA4 C17ORF76 C17ORF91 DSC2 GPT2 SGK1 FAM13A UNC5C RND3 EIF4E3 AOX1 C17ORF59 NCOR1 MT1E LOC283267 C20ORF56 C4ORF37 MT1L PTH1R KIF4CP CLN8 TEX11 LDHD PITPNM3 FAM82A1 AMT NHEDC1 KCNIP4 VPS4B MFSD6L SMAD4 HSD17B2 C21ORF33 LRRC30 CYB5A MAPK10 C4ORF34 SMPD1 CENPV TNXB TMEM88B MT1M LOC389033 VPS53 SLC10A6 HAPLN1 RIOK3 TMEM95 SEL1L PPP2CB MAP2K4 KIAA0125 KRTAP19-8 DHRS7C DDX60 CLTB CYB5D1 IGHA1 SCARA5 NR3C2 SULTIA1 KRTAP20-3 LOC285501 SULT1B1 STIM1 ARID1B MAOA ATP8B1 SOX15 CYB5D2 RAB27A GAB1 PLG CA2 PTP4A1 KRTAP10-9 EP400NL TNFRSF13B SQRDL SLC16A11 GBA3 PLD6 NAP1L5 SLC9A1 MAPK7 SLC39A8 SPPL2A LOC100128977 GPM6A RICH2 SECISBP2L ESR1 PLCE1 SGSM2 MST1P9 FLJ32063 PTPN21 TRPM6 ZNF286B LRIT3 HPGDS PQLC1 CHGA EVPLL HYAL1 UGDH LOC100287411 C4ORF32 PPARGC1A UGT2A3 CDRT15 TBC1D9 FUCA1 WWC2 CLEC3B ABCA8 MPDU1 LOC285878 MIER3 C17ORF74 PKIB CHL1 ADH6 ENTPD5 SETBP1 BDH2 FLJ40330 PPAP2A ACSL1 SMCHD1 TMEM88 OSBPL1A TRPV1 DHDDS SYNPO2 ZNF575 ODZ3 ACAA2 ANXA10 KIAA1211 ADH4 SMPDL3A CLEC10A ABHD3 PLA2G12A PCK1 ZSWIM7 TNFRSF11A MTTP LOC100128573 SEC24B ANKRD12 LOC100288798 ANK3 ING2 SLC30A10 AFF1 METTL7A MYOCD RUNDC3B SLC25A35 LAMA1 CXCL14 ITM2C CAMKK1 SRI DNAH9 SEMA6A HERPUD1 KIAA1468 HERC5 PPP2R3A SHPK C11ORF86 ZNF18 LPAR1 VAPA RDH5 CALM1 SYTL4 CYTL4 CNTN3 SLC17A4 AQP8 CPM FECH KLF4 LOC646627 PAG1 CYTSB MT1JP UGP2 LOC100129069 CLDN23 CA7 CHP2 SLC26A2 PAPSS2 CDKN2B LOC285758 LOC100289632 IGLV2-14 RETSAT CDH19 NKX2-3 MOBKL2B ZNF24 MOGAT2 LOC100133944 PAQR5 FTHL20 TRANK1 SOCS6 SLC25A34 LOC642513 HDHD2 ZADH2 LOC284112 RNF125 FAM59A CLDN8 AKR1B10 LOC728003 LOC100133337 CNNM4 MPPE1 IL17REL KCNK10 TTLL8 PPARGC1B PLAC2 AP3S2 PRKCB LOC100289019 TNXA TMEM37 DPF3 FXYD1 ENDOD1 FBLIM1 WDR78 CD36 FAM162A ANO5 UQCR10 CES3 LOC283435 ASXL3 ANF397OS GNA11 SLC41A2 LOC346329 AHCYL2 HHLA2 LOC653506 MMP28 LOC100132938 BTNL3 PTPRH VIPR SECTM1 SLC2A3P1 CASP7 APC LOC641367 FAM126B SLC2A13 FLJ30901 NHSL1 NR3C1 14LOC729468 S. Chakraborty KIF16B TRGC2 PDE8A PYY2 LOC100128823 ARSA GDPD3 SupplementaryCA12 File 2 (continued) TSHZ1 HOXD1 CAPN2 C5ORF30 ADD1 CNNM2 TLCD2 TRGV9 TNFRSF17 ZBTB7C HSPC159 OAF LOC100131506 MPND CHMP2 TTC38 BMP5 C1ORF201 C4ORF19 LOC100131014 ANGPTL7 APPL2 ZFYVE28 MFN2 PTGDR FAM5C PACSIN2 CFD VSIG CD177 ACO2 MARCH8 ADCY9 RNF138 CLMN TMEM100 C10ORF54 MRPL35 MBOAT1 LOC727916 CETN4P FAM150B PAFAH2 CLDN7 OSTBETA BEST2 LOC100133075 GOLM1 TSPAN3 ABCA5 TMCC3 FAM30A TEF CP NOVA1 AB13BP FNIP2 TL3 PRAMEF20 USP2 PRAMEF21 CALCOCO2 SLCO2A1 MTUS1 MIER1 MS4A12 FLVCR2 AFG3L2 KCNMA1 PRKACB PAFAH1B1 NCRNA00207 UGT1A8 TMEM82 CDKL1 FAM107B KCTD9 CPNE8 HSBP1L1 BCAR3 TST PYY DISP2 LRRC66 KCTD1 PRIMA1 KIAA0513 MTHFR SELENBP1 PRAMEF22 SFTA1P LRRC1 PRAMEF5 HSD11B2 PADI2 P2RY14 PRAMEF15 PRAMEF9 KLF13 PRAMEF13 TMEM30B PRAMEF14 FLJ227763 GCG CDC42SE2 LPCAT4 HADHA STON2 C16ORF62 IL6R LOC440563 PGM1 PPM1A PGPEP1 CTDP1 AGXT2L2 CTSG SLC25A23 LETM1 MUL1 GAK EDN3 GRAMD3 SFRP1 HEXIM1 C15ORF53 FTHL2 TRD@ SESN2 ATP13A4 POLD4 PDE5A SNAP29 LUZP1 HPSE TUBAL3 STMN2 ATG4D PLXNA2 FGFR2 STYK1 LOC391769 C18ORF32 NCF1B FMO4 MYO15B HMGCL C18ORF18 VPS13D MNMAT1 CDC14A FAM189A1 MEP1B TNFSF12-TNFS13 CTNND1 PADI6 DMXL1 RAB37 MEI1 RPS6KA1 SMG6 GIMAP1 CEACAM1 CDHR5 PLS1 PDCD6IP GCOM1

Annals of Gastroenterology 27