Integrated network and experimental analysis identifies an H. pylori –associated inflammatory gene signature in colorectal cancer

To investigate the role of H. pylori -infection associated key genes in the pathogenesis of colorectal cancer. This study is an observational study. The whole and being in silico and in vitro in nature, does not require ethical consent. Methodological pipelines include WGCNA analysis of two sizable colorectal cancer transcriptomic datasets (GSE39582 and GSE17536; n = 762), RT-qPCR analysis, Western blotting. ROC analysis, Cox regression analyses, Dual-luciferase assay, overexpression, and genes knockdown experiments. CXCL1, CXCL8, PTGS2, and MMP9 were identified as hub genes within an inflammation-associated module exhibiting a robust correlation with the H. pylori infection score. These genes exhibited considerable prognostic significance, moderate to robust diagnostic efficacy, and high expression in colorectal cancer. Their clinical significance was further substantiated by correlations with drug resistance, CNV, and epigenetic regulation. Functional assays show that these genes make colorectal cancer cells infected with H. pylori move, clone, and grow. This study identifies four inflammation-associated hub genes (CXCL1, CXCL8, PTGS2, and MMP9) correlated with H. pylori –associated transcriptional activity in colorectal cancer. These findings suggest a potential link between infection-related inflammatory signaling and tumor progression and highlight candidate biomarkers for further investigation.