Regulation of gastric cancer progression by immune-related transcription factors CEBPB in Helicobacter Pylori infection

Abstract

Helicobacter pylori infection is a primary risk factor for gastric carcinogenesis, yet the heterogeneity of host cellular responses remains incompletely characterized. This study systematically delineates the transcriptional landscapes of four gastric epithelial cell lines (AGS, GES-1, HGC-27, MKN-45) upon H. pylori infection. Transcriptomic analyses revealed distinct, cell-type-specific dysregulation patterns, with Gene Ontology enrichment highlighting perturbations in processes ranging from epidermal differentiation and metabolism (AGS) to extracellular matrix remodeling (GES-1), cell cycle control (HGC-27), and mitotic regulation (MKN-45). Intersection analysis identified a conserved core signature of 41 upregulated and 11 downregulated genes, implicating unified stress, inflammatory, and metabolic responses. From this signature, nine key transcription factors (TFs) were extracted, with CEBPB and MAFF demonstrating significant prognostic value in gastric adenocarcinoma (STAD) cohorts. Subsequent pan-cancer investigation established CEBPB as a context-dependent regulator, showing upregulation in STAD and other malignancies where its high expression correlated with poor prognosis. Mechanistically, CEBPB expression in STAD was associated with an immunosuppressive microenvironment (correlating with M2 macrophages and dendritic cells), co-expression with chemokine and checkpoint genes, and elevated metrics of genomic instability (MATH, ploidy, LOH). These findings position CEBPB as a central mediator linking H. pylori infection to oncogenic reprogramming, immune evasion, and genomic chaos in gastric cancer, offering a multifaceted target for therapeutic intervention.