Comprehensive bioinformatics analysis identifies KYNU as a novel Helicobacter pylori -associated biomarker with prognostic and therapeutic potential in gastric cancer.

Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC), yet the key genes mediating this carcinogenesis remain unclear. This study aimed to identify H. pylori-related genes in GC and elucidate their molecular functions. Transcriptomic data from TCGA and GEO databases were analyzed using weighted gene co-expression network analysis (WGCNA), LASSO regression, and multivariate Cox analysis to construct a prognostic model. The immune landscape was also assessed. Validation involved RT-qPCR and immunohistochemistry (IHC). An in vitro H. pylori co-culture system was used to assess time-dependent changes in gene and protein expression via RT-qPCR, IHC, and Western blotting. A four-gene risk model (PDCD1, KYNU, CYTL1, and FZD2) was identified, demonstrating strong predictive capacity for overall survival as an independent prognostic factor. High-risk patients exhibited reduced immune cell infiltration. CellMiner analysis identified potential therapeutic agents targeting these genes. Among them, KYNU showed significant upregulation in GC tissues. Notably, in the co-culture system, KYNU expression markedly increased at both mRNA and protein levels following H. pylori infection in a time-dependent manner. The H. pylori-associated risk model represents a novel independent prognostic indicator for GC. Particularly, KYNU emerged as a pivotal gene in H. pylori-mediated GC, offering insights into disease progression and serving as a promising therapeutic target.