Multi Omics and Mechanistic Investigation Reveals CBFB as a Prognostic Biomarker in Gastric Cancer

Background : Gastric cancer (GC) is an aggressive malignancy with poor prognosis due to complex pathogenesis, underscoring the need for biomarkers and targets. CBFB has regulatory roles across cancers and shows promise, but its prognostic significance and mechanisms in GC remain unclear. Methods : We analyzed GC transcriptomes by WGCNA to identify modules; machine learning prioritized core regulators. GSEA predicted signaling pathways, and molecular docking validated CBFB–STAT3 interactions. Single-cell RNA-seq was processed with Seurat for QC, clustering, and annotation; CellChat quantified intercellular ligand–receptor crosstalk. Functional validation employed CCK-8 proliferation and Transwell migration/invasion assays; Western blot assessed pathway activity. Results : Multi-omics analyses implicate CBFB in GC pathogenesis. WGCNA highlighted 40 ribosome biogenesis–related genes, with machine learning prioritizing CBFB as a key regulator. GSEA linked CBFB to the JAK/STAT pathway (NES 1.95). Docking showed high-affinity CBFB–STAT3 binding (ΔG −11.5 kcal/mol). scRNA-seq showed higher CBFB in tumor parenchyma, enriched in mast cells; CellChat revealed enhanced mast cell–endothelial crosstalk via COL4A1/COL4A2–CD44 in CBFB-high groups (P<0.01). Functionally, CBFB knockdown reduced proliferation by ~40% and invasion/migration by ~30% (P<0.01); Western blot showed decreased STAT3 phosphorylation and reduced MMP9, implicating a CBFB–STAT3–MMP9 axis in GC progression. Conclusion : CBFB acts as a pivotal GC oncogene, with higher expression predicting poor prognosis and showing strong diagnostic potential. Mechanistically, CBFB may promote progression by engaging STAT3; single-cell data indicate overexpression in mast cells with enhanced mast cell–endothelial crosstalk. Functional data support CBFB as a therapeutic target in GC.