Identification of MIG7, TGM2, CXCL8, and PDGFC as Key Genes in Colon Cancer with a Bioinformatics-Driven strategy for Multi-Epitope Vaccine Design
Abstract
Colon cancer (CRC) patients are often analyzed at advanced stages with poor diagnosis. This study sought to recognize potential diagnostic and prognostic biomarkers for CRC using RNA sequencing data (GSE119947, GSE266390, and GSE180948) from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were analyzed using GEO2R, and key DEGs were further examined through GO and KEGG enrichment studies. Protein-protein interaction (PPI) networks were constructed using Cytoscape, identifying hub genes which were then evaluated with Kaplan–Meier survival analysis in the GEPIA database. GO analysis revealed significant enrichment in apoptosis, cell proliferation, and adhesion, while KEGG analysis highlighted the PI3K-Akt signaling pathway and extracellular matrix-receptor interaction as prominent pathways. Notably, CXCL8, TGM2, PDGFC, and MIG7 were significantly upregulated in colorectal tumors and associated with better survival. These findings suggest that CXCL8, TGM2, PDGFC, and MIG7 could serve as biomarkers for CRC diagnosis, prognosis, and vaccine development. A novel multi-epitope peptide vaccine incorporating these proteins was designed, featuring immune-dominant regions fused with linkers and adjuvants to enhance immunogenicity. The vaccine's stability and potential to induce both humoral and cellular responses were supported by docking and dynamics simulations. This study indicates that the proposed vaccine could be a promising therapeutic option for CRC.