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The Expression Patterns and the Diagnostic/Prognostic Roles of PTPN

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The Expression Patterns and the Diagnostic/Prognostic Roles of PTPN Chen et al. Cancer Cell Int (2020) 20:238 https://doi.org/10.1186/s12935-020-01315-7 Cancer Cell International PRIMARY RESEARCH Open Access The expression patterns and the diagnostic/ prognostic roles of PTPN family members in digestive tract cancers Jing Chen1,2,3, Xu Zhao4, Yuan Yuan1,2,3* and Jing‑Jing Jing1,2,3* Abstract Background: Non‑receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phos‑ phorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers. Methods: Oncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene–gene interaction network was performed by GeneMA‑ NIA and the protein–protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of diferentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verifcation, the expression of four PTPNs in digestive tract cancers were further analyzed. Results: Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. Several PTPN members were diferentially expressed in digestive tract cancers. For esophageal carci‑ noma (ESCA), PTPN1 and PTPN12 levels were correlated with incidence; PTPN20 was associated with poor progno‑ sis. For stomach adenocarcinoma (STAD), PTPN2 and PTPN12 levels were correlated with incidence; PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23 were correlated with pathological grade; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 implied worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colorectal cancer (CRC), PTPN2, PTPN21 and PTPN22 levels were correlated with incidence; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verifcation experiment showed diferential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC. Conclusions: Members of PTPN family were diferentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated *Correspondence: [email protected]; [email protected] 1 Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No. 155 North NanjingBei Street, Heping District, Shenyang 110001, Liaoning, People’s Republic of China Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Chen et al. Cancer Cell Int (2020) 20:238 Page 2 of 15 in both STAD and CRC, and thus could be used as a diagnostic biomarker. Diferential expression of PTPN12 in GC and CRC, and PTPN22 in CRC were presented in our histological verifcation experiment. Keywords: PTPN family members, Digestive tract cancers, Expression, Diagnosis, Prognosis, Clinical features Background the clinical value of diferent PTPN genes to support Tyrosyl phosphorylation is a dynamic and reversible pro- potential biomarkers and new individualized targets for cess which plays a pivotal part in many cellular signaling patients. In the current study, we analyzed the expression pathways [1]. Te dephosphorylation of tyrosine resi- status of diferent PTPN members and their diagnostic dues are catalyzed by a series of enzymes named protein and prognostic values to comprehensively evaluate the tyrosine phosphatases (PTPs) [2]. Encoded by 103 genes, role of PTPNs in various digestive tract cancers. PTPs are sorted into four major superfamily classes [3], and every single PTP was denominated an ofcial gene Methods name by Te Human Genome Organization in Nomen- Oncomine database analysis for the expression patterns clature Committee. According to the latter system, 17 of PTPN family in digestive tract cancers non-receptor PTPs which belong to the biggest family Oncomine database is a cancer microarray database class I, are designated PTPN, followed by a number [3]. (https ://www.oncom ine.org/) which shows the expres- Tere is mounting evidence suggesting that the cross-talk sion information of genes in cancer and normal samples of the PTPN gene family members is involved in exten- [13]. Oncomine provides both microarray information sive physiological processes, such as cell proliferation, from 715 datasets and a set of online data-mining func- survival, immune response, migration, and metabolism tions. Te expression levels of individual PTPN family [3–6]. Previously published study stated that PTPN fam- members in diferent types of cancer were obtained from ily members play an essential part in numerous diseases. the Oncomine database. Student’s t test was applied to For example, the expression of PTPN6 with the loss of calculate the P value for expression diferences of PTPN pSTAT3 expression could be chosen as a biomarker for family genes between normal controls and cancer sam- the prognosis of peripheral-T cell lymphoma [7]. One ples. Te threshold parameters of P value and fold change research published recently noted that a defciency of were demarcated as 0.05 and 2 respectively. PTPN2 could enhance anti-tumor immunity and the therapeutic efcacy of CAR T cells to solid cancers [8]. Ualcan database analysis for the validation PTPN22 plays an important part in regulating autophagy Ualcan is a publicly available web-portal (http://ualca and NLR family pyrin domain containing 3 infamma- n.path.uab.edu) that ofers online analysis of data from some activation [9]. It is hopeful that PTPN genes have Te Cancer Genome Atlas (TCGA) [14]. In this study, we potential to be served as prognostic and diagnostic indi- used it to analyze the relative expression of PTPN family cators [10], and even therapeutic targets. genes in esophageal carcinoma (ESCA), stomach adeno- As main malignancies of gastrointestinal tract, esoph- carcinoma (STAD), colon adenocarcinoma (COAD), agus cancer (EC), gastric cancer (GC) and colorectal rectum adenocarcinoma (READ) and normal samples. cancer (CRC) are responsible for a large portion of can- Te expression level of PTPN members was normalized cer-related deaths worldwide, of which the data are 5.3%, as transcript per million reads, and a P value of no more 8.2% and 9.0% respectively [11]. All of the three diges- than 0.01 conducted through Student’s t test was consid- tive tract cancers are ranked in the top 10 for incidence ered to be signifcant. rates of tumors and have poor prognosis [11]. Although a couple of diagnostic biomarkers have been observed, TCGA data obtainment through UCSC Xena robust biomarkers to predict clinical outcomes are still Te Cancer Genome Atlas (TCGA) is a cancer genomics in urgent need [12]. Former investigations reported that database (https ://cance rgeno me.nih.gov/) which contains the expression patterns of individual PTPNs and its cor- genomic information of over 2000 primary neoplasms relations with patients in various digestive tract neo- and matched normal samples [15, 16]. In our study, case plasms, but research to date has not yet observed the information concerning the mRNA expression profles whole picture of the entire PTPN family, from the aspects and clinical features were obtained from TCGA database, of diagnosis, prognosis and expression characteristics. which was downloaded through the University of Cali- Personalized therapies based upon the genetics of indi- fornia Santa Cruz Xena (UCSC Xena; https ://xena.ucsc. vidual cancer will be prior to other treatments in the near edu/) platform [17]. Data of 184 ESCA and 11 matched future. Tis research therefore is intended to illuminate normal
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