Evaluation of Epithelial-Mesenchymal Transition Genes Involved in Iranian Gastric Cancer Patients via Transcriptome Analysis

Background: Gastric cancer is one of the most frequent cancers among men and women. Patients with gastric cancer are mostly diagnosed in advanced stages because of asymptomatic progression. Due to the heterogeneity and poor prognosis of this cancer, a comprehensive study at the transcriptome level gene expression is needed to find the various genes and mechanisms involved in gastric cancer. Differentially expressed genes (DEG) derived from high-throughput RNA-sequencing could lead to the achievement of new molecular biomarkers. Objectives: In this study, after transcriptome reanalysis, we focused on the genes involved in epithelial-mesenchymal transition (EMT) via extracellular matrix (ECM). We have aimed at finding mRNA level changes in new candidate genes among Iranian patients with gastric cancer. Methods: Six gastric cancer and two normal sequencing raw sample datasets were collected from the European Nucleotide Archive (ENA). The bioinformatic pipeline was used to reanalyze raw datasets and get DEGs, using the DESeq2 package. After analyzing, THBS2, OSMR, and CHI3L1 genes were selected for validation and verification in 25 confirmed adenocarcinoma gastric cancer patients and non-malignant normal tissues from the Iranian population by real-time polymerase chain reaction (PCR). Results: The bioinformatic analysis of raw datasets revealed many upregulated and downregulated genes in gastric cancer tissues compared with normal samples. Then, real-time PCR verified the upregulation of THBS2, OSMR, and CHI3L1 genes in a group of Iranian patients with gastric cancer. Analyzing graphs showed a significant increase in the expression of targeted genes in patients with gastric cancer (P 0.0001, P = 0.0016, and P = 0.0002, respectively). Conclusions: The results validated an obvious increase in the expression of THBS2, OSMR, and CHI3L1 genes in gastric cancer of Iranian patients. These genes are involved in EMT and may have a role in cancer invasion if tested further for their diagnostic and prognostic value in larger sample sizes.