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Background <p>Gastric cancer is an aggressive malignancy with poor prognosis due to complex pathogenesis, underscoring the need for biomarkers and targets. Core Binding Factor Beta Subunit (CBFB) has regulatory roles across cancers and shows promise, but its prognostic significance and mechanisms in gastric cancer remain unclear.</p> Methods <p>We analyzed Gastric cancer transcriptomes by Weighted Gene Co-expression Network Analysis(WGCNA) to identify modules; machine learning prioritized core regulators. Gene Set Enrichment Analysis predicted signaling pathways, and molecular docking validated Core Binding Factor Beta Subunit–Signal Transducer And Activator Of Transcription 3(CBFB-STAT3) interactions. Single-cell RNA-seq was processed with Seurat for Quality control, clustering, and annotation; CellChat quantified intercellular ligand–receptor crosstalk. Functional validation employed Cell Counting Kit-8 proliferation and Transwell migration/invasion assays; Western blot assessed pathway activity.</p> Results <p>Multi-omics analyses implicate CBFB in gastric cancer 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). Molecular docking further revealed a high binding affinity between CBFB and STAT3 (ΔG − 11.5&#xa0;kcal/mol), suggesting a potential interaction. scRNA-seq demonstrated higher CBFB expression in tumor parenchyma, particularly enriched in mast cells. CellChat analysis revealed enhanced mast cell–endothelial crosstalk via COL4A1/COL4A2–CD44 in CBFB-high groups (<i>p</i> &lt; 0.01). Functionally, CBFB knockdown reduced proliferation by ~ 40% and invasion/migration by ~ 30%. Western blot analysis further showed decreased STAT3 phosphorylation and reduced MMP9, suggesting a functional link within a CBFB–STAT3–MMP9 axis crucial for gastric cancer progression.</p> Conclusion <p>CBFB acts as a key player in Gastric cancer progression, 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 Gastric cancer.</p> Graphical Abstract <p></p>

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Multi omics and mechanistic investigation reveals CBFB as a prognostic biomarker in gastric cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Qi Zhou,
  • Lu Wang,
  • Meng-Han Wang,
  • Yao-Hong Yuan,
  • Jian Guo,
  • Bo Chen,
  • Ji-Zhe Zhang,
  • Mi-Zhu Wang

摘要

Background

Gastric cancer is an aggressive malignancy with poor prognosis due to complex pathogenesis, underscoring the need for biomarkers and targets. Core Binding Factor Beta Subunit (CBFB) has regulatory roles across cancers and shows promise, but its prognostic significance and mechanisms in gastric cancer remain unclear.

Methods

We analyzed Gastric cancer transcriptomes by Weighted Gene Co-expression Network Analysis(WGCNA) to identify modules; machine learning prioritized core regulators. Gene Set Enrichment Analysis predicted signaling pathways, and molecular docking validated Core Binding Factor Beta Subunit–Signal Transducer And Activator Of Transcription 3(CBFB-STAT3) interactions. Single-cell RNA-seq was processed with Seurat for Quality control, clustering, and annotation; CellChat quantified intercellular ligand–receptor crosstalk. Functional validation employed Cell Counting Kit-8 proliferation and Transwell migration/invasion assays; Western blot assessed pathway activity.

Results

Multi-omics analyses implicate CBFB in gastric cancer 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). Molecular docking further revealed a high binding affinity between CBFB and STAT3 (ΔG − 11.5 kcal/mol), suggesting a potential interaction. scRNA-seq demonstrated higher CBFB expression in tumor parenchyma, particularly enriched in mast cells. CellChat analysis 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%. Western blot analysis further showed decreased STAT3 phosphorylation and reduced MMP9, suggesting a functional link within a CBFB–STAT3–MMP9 axis crucial for gastric cancer progression.

Conclusion

CBFB acts as a key player in Gastric cancer progression, 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 Gastric cancer.

Graphical Abstract