مقالات پذیرفته شده در پنجمین کنگره بین المللی زیست پزشکی
Evaluation of miR-551 and miR-6 as Diagnostic and Therapeutic Biomarkers for Gastric Cancer Associated with Helicobacter Pylori with Bioinformatics Approach
Evaluation of miR-551 and miR-6 as Diagnostic and Therapeutic Biomarkers for Gastric Cancer Associated with Helicobacter Pylori with Bioinformatics Approach
Sara Fakharian Kashani,1Zainab Abedini,2Aynaz Farhang Darehshouri,3Kimia Jazi,4Hamid Taghvaei Javanshir,5Ahmad Bereimipour,6,*
1. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran 2. Medical Genomics Research Center, Tehran Medical Sciences Islamic Azad University, Tehran, Iran 3. Medical Genomics Research Center, Tehran Medical Sciences Islamic Azad University, Tehran, Iran 4. Student research committee, faculty of medicine, medical university of Qom, Qom, Iran 5. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran 6. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Introduction: Gastric cancer is the 6th most prevalent cancer in the world (1). Although the worldwide mortality rates stand the 5th, gastric cancer rates 3rd and 1st in prevalence and mortality respectively among the Iranian population (1). Helicobacter pylori (HP) as a group 1 or definite carcinogen(2). HP releases urease, protease, phospholipase, ammonium, and acetaldehyde and thus disturbs the gastric mucosal barrier; moreover, it induces reactive oxygen production and suppresses the antioxidant defense mechanisms of the host, and result in oxidative damage (3). Furthermore, HP could cause gastric cancer by increasing endogenous DNA damage, reducing nuclear and mitochondrial mutation, and repairing DNA activity, resulting in aberrant DNA methylation (4). To reveal treatments and early-screening strategies, this study intended to evaluate the genes, functioning proteins, and related miRNAs through which HP provokes gastric cancer to track gene expression patterns, miRNA expression regulations, and active proteins and reveal potential therapy targets.
Methods: This investigation relied on bioinformatics analysis. Based on this, the GEO database was used to find the microarray gene expression profile. For this purpose, gastric cancer datasets GSE65801 without Helicobacter pylori and GSE116312 with Helicobacter pylori were chosen. The GEO 2 R analysis was then completed, followed by the Venn tool subscriptions. The signaling pathway was created using the Enrichr database, and molecular function and biological process data were found in the GO database. As a result, the Hub genes were discovered using the STRING tool. The miRTarBase database was also used to identify miRNAs.
Results: The result of the analysis shows that 77 genes with high expression and 89 genes with low expression were classified as gastric cancer genes with helicobacter pylori infection. Negative regulation of interleukin-5 product, EGFR/EGF signaling pathway wp437, Activation of the Ap-1 family of transcription factors Homosapiens R-HAS-450341, and Negative regulation of activated T cell proliferation were observed in low expression genes. In the overexpressed gene, we observed protein serine/threonine kinase activator activity, Protein phosphatase activator activity, External encapsulating structure organization, and Regulation of T-helper 1 cell cytokine production as signaling pathways. EGFR, PTK2, EPHB2, HOXA7 proteins are significantly associated with downregulated genes, and CALR, Hist1H31, Hist1H3f, Hist1H4h, Hist1H2BB is related to upregulated genes. And among these proteins hsa- miR-551, hsa- miR-1, hsa- miR-6 were significantly associated with more genes.
Conclusion: In general, bioinformatics analysis can more accurately assess the relationship between gastric cancer with Helicobacter pylori infection. Selecting a panel of appropriate biomarkers present in the extracellular matrix and extracted through various human flows is the right solution for early detection, followed by proper treatment management and mortality reduction. This study focuses on EGFR, PTK2, EPHB2, HIST1H3F, HIS1H4H, proteins and hsa-miR-6, hsa- miR-551 miRNA released into the extracellular matrix provided various biomarkers for stages of gastric cancer, which require more extensive studies to investigate and find more precise mechanisms of these proteins.