Identification of differentially expressed genes (DEGs) in pancreatic adenocarcinoma using bioinformatics and systems biology analyzes and evaluating the effect of common chemotherapy drugs on the expression pattern of key genes in pancreatic cancer cells as potential diagnostic and therapeutic targets

Abstract

Pancreatic cancer is a highly dangerous disease associated with high mortality rates. Due to its high prevalence and challenging early-stage diagnosis, it is often detected in advanced stages, with limited effective treatments available. Common symptoms of pancreatic cancer include biliary obstruction, gastrointestinal problems, weight loss due to decreased appetite, and weakened immune system. The survival rate among pancreatic cancer patients is very low, and most individuals succumb shortly after diagnosis. The aim of this study is to identify the altered genes (DEGs) in pancreatic adenocarcinoma using bioinformatics and systems biology analyzes and to evaluate the effect of common chemotherapy drugs on the expression pattern of key genes in pancreatic cancer cells as targets. It is capable of diagnosis and treatment, which is necessary to explain more effective diagnostic and treatment methods for better management of pancreatic cancer and also to improve the survival of patients. Methods: In this study, existing microarray data from the GEO database with the specific code GSE28735 was initially used for comparison to profile gene expression in tumor samples from pancreatic cancer patients against normal samples. Using online tools, differentially expressed genes (DEGs) were identified. Subsequently, a gene co-expression network was constructed using the STRING database, and genes with the highest interaction and degree in this network were selected for further study. To validate these genes, pancreatic cancer cells were treated with the chemotherapeutic drugs 5-fluorouracil and oxaliplatin. Following treatment, RNA was extracted from both the treated and control cells, and cDNA was synthesized. The expression of the identified genes was then examined using Real-Time PCR. The results of the gene expression analysis and comparison with the control group were assessed using specialized statistical software, such as GraphPad Prism and t-test. In all statistical tests, a P value of less than 0.05 was considered significant. Results: The results of this study indicate that the chemotherapeutic drugs oxaliplatin and fluorouracil have a significant ability to reduce the viability of pancreatic cancer cells. Additionally, it was observed that these drugs, especially their combination, lead to a significant decrease in the expression of ITGB1 and LAMC2 genes, which are important genes involved in the pathogenesis of pancreatic cancer.