Investigation of system biology analysis of gastric cancer (GC) patients and evaluating the expression of obtained differentially expressed genes in GC cell line treated with chemo-drugs

Abstract

Gastric cancer is considered a global health problem and recently more than 1 million people around the world are diagnosed with this type of cancer. Despite a global decrease in incidence and mortality over the past 5 decades, gastric cancer remains the third leading cause of cancer-related death. Factors such as late diagnosis and resistance to current treatment methods are among the main factors of the high mortality rate of this malignancy. Therefore, it is necessary to identify new targets and molecular pathways to develop new and targeted treatment methods. Materials and Methods: In this study, we identified the genes involved in the occurrence of gastric cancer using bioinformatics and analyzed the effect of common chemotherapy drugs on their expression. Using the datasets available in the GEO database, the genes that undergo changes in expression in gastric cancer were identified. Then, gastric cancer AGS cells were treated with paclitaxel and 5-FU and their IC50 values were measured. Also, the RNA content of treated cells and untreated control cells were extracted, and after cDNA synthesis, the expression of identified genes was analyzed by Real-Time PCR method. Results: Bioinformatics analysis using GSE33335 dataset showed that ANXA10, ATP4A, LUM, PCG and CA9 are among the genes whose significant expression changes can play a role in the development and progression of gastric cancer. Also, the results of Real-Time PCR showed that ANXA10 gene expression increases significantly after treatment with paclitaxel, while treatment with 5-FU did not change its expression. On the other hand, ATP4A was significantly increased in the treatment with 5-FU, but the treatment with paclitaxel did not change the expression of this gene. Also, the change in CA9 gene expression was not significant with the mentioned treatments. On the contrary, the expression of LUM, PGC genes in the treated groups significantly decreased and increased, respectively.