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Screening Differentially Expressed Genes of Pancreatic Cancer Between Mongolian and Han People Using Bioinformatics Technology

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Screening differentially expressed genes of pancreatic cancer between Mongolian and Han people using bioinformatics technology Jiasheng Xu First Aliated Hospital of Nanchang University Kaili Liao Second Aliated Hospital of Nanchang University ZHONGHUA FU First Aliated Hospital of Nanchang University ZHENFANG XIONG ( [email protected] ) The First Aliated Hospital of Nanchang University https://orcid.org/0000-0003-2062-9204 Research article Keywords: Pancreatic ductal cell carcinoma, Affymetrix gene expression prole, Gene differential expression, GO analysis, Pathway analysis, Mongolian Posted Date: July 9th, 2019 DOI: https://doi.org/10.21203/rs.2.11118/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Version of Record: A version of this preprint was published at BMC Cancer on April 9th, 2020. See the published version at https://doi.org/10.1186/s12885-020-06722-7. Page 1/18 Abstract Objective To screen and analyze differentially expressed genes in pancreatic carcinoma tissues taken from Mongolian and Han patients by Affymetrix Genechip. Methods: Pancreatic ductal cell carcinoma tissues were collected from the Mongolian and Han patients undergoing resection in the Second Aliated Hospital of Nanchang University during March 2015 to May 2018 and the total RNA was extracted. Differentially expressed genes were selected from the total RNA qualied by Nanodrop 2000 and Agilent 2100 using Affymetrix and a cartogram was drawn; The gene ontology (GO) analysis and Pathway analysis were used for the collection and analysis of biological information of these differentially expressed genes. Finally, some differentially expressed genes were veried by real-time PCR. Results Through the microarray analysis of gene expression, 970 differentially expressed genes were detected by comparing pancreatic cancer tissue samples between Mongolian and Han patients. A total of 257 genes were signicantly up-regulated in pancreatic cancer tissue samples in Mongolian patients;while a total of 713 genes were down-regulated. In the Gene Ontology database, 815 differentially expressed genes were identied with clear GO classication, and CPB1 gene had the highest multiple of differential expression (difference multiple: 31.76). The Pathway analysis detected 28 signaling pathways that included these differentially expressed genes, involving a total of 178 genes. Among these pathways, the enrichment of differentially expressed genes in the FAK signaling pathway was the highest and COL11A1 gene had the highest multiple difference (multiple difference: 5.02). The expressions of differentially expressed genes CPB1, COL11A1ITGA4BIRC3PAK4CPA1 CLPSPIK3CG and HLA-DPA1 determined by real-time PCR were consistent with the results of gene chip analysis. Conclusions The results of microarray analysis of gene expression proles showed that there are a large number of differentially expressed genes in pancreatic cancer tissue samples compared between Mongolian and Han populations. These genes are closely related to the proliferation, differentiation, invasion and metastasis and multi-drug resistance of pancreatic cancer and are involved in the regulation of multiple important signaling pathways in organisms. Introduction Pancreatic cancer is one of the highest mortality of digestive system malignancies. Its onset is occult, rapid progress, most patients have been found late, lost the best treatment opportunities, therefore, the search for specic and sensitive early diagnostic tools for it is particularly important to improve the prognosis of patients with pancreatic cancer and prolong their survival time [1].With the completion of the complete nucleotide sequencing of the Human Genome Project, especially the mature gene chip technology in recent years, providing a large amount of data information for high-throughput analysis of the occurrence and development of tumors, making genetic diagnosis an ideal early diagnosis of most tumors. Method [2] can elucidate the molecular mechanism of pancreatic cancer by analyzing the genes involved in the generation and maintenance of malignant biological characteristics of pancreatic cancer.In this study, Affymetrix Gene Expression Proling microarray was used to screen differentially expressed genes in Mongolian and Han pancreatic cancer samples for further gene function analysis, in order to provide important reference data and experimental evidence for the elucidation of the molecular mechanism of pancreatic cancer development. 1 Materials And Methods 1.1 Reagents and Instruments The required reagents Agilent RNA 6000 Nano Kit, GeneChip 3'IVT Express Kit, GeneChip Hybridization Wash and Stain Kit, Trizol Kit, and QIAGEN RNeasy Total RNA Isolation kit were provided by Gekkai Gene Technology Co., Ltd. The main instruments used in the study included the Thremo Nanodrop 2000, Agilent 2100, GeneChip Hybridization Oven 645, GeneChip Fluidics Station 450, and GeneChip Scanner 3000. 1.2 Research sample Page 2/18 A total of 96 fresh tumor tissue specimens from patients with pancreatic malignancies surgically resected from the Second Aliated Hospital of Nanchang University from March 2015 to May 2018 were collected, and 66 of them were initially selected according to the following inclusion and exclusion criteria. Research specimens for follow-up gene expression microarray assays. Inclusion criteria: (1) Pathologically conrmed pancreatic ductal cell carcinoma; (2) New cases diagnosed by this hospital for the rst time; (3) Patients aged ≥ 18 years; (4) Patients and their families agree to receive tissue specimens And for scientic research, allowing the exchange of research data published. Exclusion criteria: (1) local vascular invasion and regional lymph node metastasis conrmed by pathology; (2) distant metastasis found by relevant examinations or intraoperative exploration in our hospital; (3) with other malignant tumors or diabetes, hypertension Systemic diseases such as cardiovascular and cerebrovascular diseases; (4) patients who have received radiotherapy, chemotherapy, or other anti-neoplastic drugs before surgery; (5) history of surgery in the past three years. General information of patients: Of the 66 patients, 32 were Mongolian and 34 were Han; There were 34 males and 32 females; the average age was 60.12 and the youngest was 42 years old. The highest was 73 years; 24 cases were well-differentiated, 38 cases were moderately differentiated, and 4 cases were poorly differentiated. 1.3 Sample Total RNA Extraction and Quality Assurance The above collected samples were extracted and puried by Trizol kit and QIAGEN RNeasy Total RNA Isolation kit. Total RNA was obtained from the samples. Samples were tested using Nanodrop 2000 and Agilent 2100 instruments. Sample RNA concentrations, A260 and A280 values, RIN were used. Values and 28S/18S values were used to evaluate the samples. When the samples met both 1.7< A260/A280 <2.2, RIN<A26 and 28S/18S> 0.7, the samples were qualied. The above procedures were strictly followed with the reagent and instrument instructions. 1.4 Gene Chip Hybridization The double-stranded cDNA template was synthesized by mixing the puried total RNA with the internal reference poly-A RNA according to the instructions of the GeneChip 3′ IVT Express Kit kit, and the biotin-labeled aRNA was obtained by reverse transcription in vitro. (Amplied RNA) Purication of aRNA using a purication reagent in the kit and fragmentation thereof to prepare a hybridization reaction solution. The hybridization reaction solution is heated at 98° C. for 10 min, heated to 45° C. for 3 min, and then retained at 45° C., while the kit is 130 μL of the pre-hybridization solution was injected into the chip and pre-hybridized in the hybridization oven at 45°C for 10 min. After the pre-hybridization solution was discarded, 130 μL of the hybridization reaction solution was injected into the chip at 45°C and the hybridization was performed at 60 rpm for 16 h to complete hybridization. Afterwards, automatic washing was performed using the GeneChip Fluidics Station 450 instrument. Scanning was performed after the dyeing was completed to obtain data. 1.5 Real-time quantitative PCR verication The top 10 differentially expressed genes were screened for pancreatic cancer tissue and its adjacent normal tissues, and primers were synthesized according to the PCR primer information provided by the Primer Bank database (Table 1). GAPDH was used as an internal reference and a two-step method was used. The real-time PCR kit was used to detect the expression of these genes in pancreatic cancer tissues and their adjacent normal tissues and to draw statistical charts. The reaction procedure was: Hol d (pre-denaturation): 95°C, 30 s, 1 cycle; Two-step PCR: 95 °C, 5 s, 60 °C, 30 s, 40 cycles; Dissociation: 95 °C, 15 s, 60 °C, 30 s, 95 °C, 15 s, 1 cycle. Page 3/18 1.6 Data Processing and Statistical Analysis The data obtained by the above scan is analyzed using the R-Project software as follows: (1)Filter the chip as the background noise within the 20% range with the lowest signal strength of all chip probes; (2)Using the software to plot the signal intensity distribution of the gene chip probe and the relative logarithm of the probe signal intensity. Box line diagram to evaluate the reliability and repeatability of the detection results of the differential expression prole chip; (3)Gene differential expression analysis was performed using the GCBI online analysis tool (https://www.gcbi.com.cn/gclib/html/index).GCBI
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