Identification of core immune-related genes CTSK, C3, and IFITM1 for diagnosing Helicobacter pylori infection-associated gastric cancer through transcriptomic analysis.

Objectives: To identify diagnostic genes and mechanisms linking Helicobacter pylori (H. pylori) infection to gastric cancer.

Methods: Gene expression profiles from GEO were analyzed using differential expression gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and functional enrichment. A random forest (RF) model assessed immune-related diagnostic genes, examining their expression, diagnostic performance, prognostic value, and immune cell relationships. Expression patterns of core genes were evaluated with single-cell RNA sequencing (scRNA-seq), and a regulatory network involving miRNA, mRNA, and transcription factors was built.

Results: We identified 75 genes and developed an RF model including 15 immune-related genes, notably CTSK, NR4A3, C3, and IFITM1. Except for NR4A3, these genes showed higher expression in datasets, confirmed by in vitro tests. Their diagnostic performance had an AUC > 0.7, enhancing to >0.85 in a multi-gene model. Survival analysis linked gene upregulation to poorer prognosis, and scRNA-seq and immune cell infiltration analysis underscored their roles in immune dysregulation and pathogenicity in H. pylori-related gastric cancer.

Conclusions: CTSK, C3, and IFITM1 are crucial in H. pylori-related gastric cancer, forming a robust diagnostic model and guiding future diagnostic and therapeutic research.