Assessing Clinical Relevance of Gastric Cancer Cell Lines as Tumor Models by Identifying Key Genes and miRNAs involved in EMT Metastasis Pathway

Abstract

Cancer cell lines are in-vitro cancer cell models that continue to divide and proliferate under controlled laboratory conditions. They are used in medical research to study tumor pathology and for testing therapeutics efficacy. Despite their extensive application, significant differences in genetic and transcriptomic expression exist between cell lines and tumor cells. The purpose of this study was to identify the relevance of gastric cancer cell lines as suitable models for gastric tumor research. Using a two-tiered bioinformatics approach- a comparison between the gastric tumor and the gastric cancer cell line was performed using functional genomics data available in the literature to identify the common Differentially Expressed Genes (DEGs). The study revealed differential expression of a total 380 genes common in both gastric cancer cell lines and tumor samples. Interestingly, four of these genes were identified as the Epithelial Mesenchymal Transition (EMT) markers, involved in the accelerated metastasis, of which two genes with discrete over-expression patterns, namely- ITGB1 and TGFB1 were selected for further analysis. Their survival analysis revealed their key role in gastric cancer severity, evident by the regressed survival rate of gastric cancer patients upon their overexpression. A total of nine tumor-suppressor miRNAs relevant to ITGB1 and TGFB1 were also identified. In conclusion, our findings indicate that inspite of various genetic and transcriptomic deviations, the tumor and cell line exhibit comparable expression patterns. The data obtained would be useful to implore the druggability of these targets with a goal of improved translational rates.