Integrated Transcriptomic Analysis Identifies Hub Genes and Dysregulated Signaling Pathways in Gallbladder Cancer

Abstract

Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract associated with poor prognosis, largely due to late-stage diagnosis and the lack of effective targeted therapeutic options. Comprehensive elucidation of the molecular mechanisms underlying gallbladder carcinogenesis and the identification of key regulatory genes and signaling pathways are therefore critical for the development of improved diagnostic and therapeutic strategies. Integrated transcriptomic analysis provides a powerful approach for identifying differentially expressed genes (DEGs) and deciphering their associated molecular networks. In the present study, gene expression profiles from two independent Gene Expression Omnibus (GEO) datasets, GSE100363 and GSE139682, were analysed to identify molecular signatures associated with gallbladder cancer. A total of 26 samples, comprising 13 gallbladder cancer tissues and 13 normal gallbladder controls, were included. Differential expression analysis was performed independently for each dataset using the GEO2R tool, applying stringent statistical thresholds of adjusted p-value < 0.05 and log₂ fold change criteria. Protein–protein interaction network analysis was subsequently performed, and the top ten hub genes were identified using the cytoHubba plugin in Cytoscape. Functional enrichment analysis of the overlapping DEGs was conducted using KEGG pathway analysis via Enrichr. The analysis revealed extensive transcriptional dysregulation in gallbladder cancer. Notably, GPRIN2, H1-5, ERBB2, KRT17, MAL2, GRB7, PLEK2, CLDN4, LAMB3, and ESRP1 emerged as key upregulated hub genes. KEGG pathway enrichment analysis demonstrated significant involvement of cancer-related pathways, including PI3K–Akt signaling, focal adhesion, integrin signaling, tight junctions, and cornified envelope formation, reflecting disruptions in epithelial integrity, cell–matrix interactions, and survival signaling. In conclusion, this integrative bioinformatics approach identifies critical hub genes and dysregulated signaling pathways that contribute to gallbladder cancer pathogenesis, providing valuable insights into disease mechanisms and highlighting potential biomarkers and therapeutic targets.