Integrated RNA-sequencing and network analysis approach to identify the Hub genes and vital pathways associated with gastric cancer

Abstract

Context: Gastric cancer is one of the most prevalent types of cancer in developing countries and ranks fourth in terms of death causes. Helicobacter pylori infection is a significant contributor to the emergence of gastric cancer. Lack of early diagnosis of gastric cancer is a leading cause of death. Aims: To identify the key genes and pathways involved in gastric cancer. Methods: This study performed a comprehensive analysis of RNA-Seq data from human gastric cancer and adjacent normal tissues. Raw data passed quality checks with FastQC and were aligned to GRCh38 using HISAT2. Subread's FeatureCounts handled transcript assembly and quantification. DESeq2 pinpointed significant genes, while ClueGO explored gene ontology and KEGG pathways. Protein-protein interaction networks, constructed with StringApp, aided in identifying hub genes through CytoHubba. This holistic approach yields insights into the molecular mechanisms underpinning gastric cancer. Results: This study detected 711 differentially expressed genes (DEGs) between normal and gastric samples. A total of 594 genes were identified as upregulated and 117 as downregulated. Major DEGs are enriched in signal transduction, stimulus-response regulation, transmembrane signaling receptor activity, and signal transduction pathways involving cytokines. In addition, 20 hub genes from the PPI network were identified based on MCC rank analysis from the CytoHubba plugin, contributing to the progression of gastric cancer. Conclusions: The top six hub genes, CD4, CTLA4, CD28, CD80, CD27, and SELL, are expected to regulate several pathways and may serve as potential biomarkers for the early detection and treatment of gastric cancer patients.