TGFB2 serves as a link between epithelial-mesenchymal transition and tumor mutation burden in gastric cancer

Area of Science:

• Oncology
• Cancer Immunology
• Molecular Biology

Background:

• Immune checkpoint blockade (ICB) shows promise in gastric cancer (GC), but poor outcomes persist.
• Epithelial-mesenchymal transition (EMT) is linked to reduced ICB response, potentially via tumor mutational burden (TMB) modulation.
• The role of transforming growth factor beta 2 (TGFB2) in driving EMT and its impact on TMB in GC remains unclear.

Purpose of the Study:

• To investigate the role of TGFB2 in gastric cancer (GC) progression and its association with epithelial-mesenchymal transition (EMT) and tumor mutational burden (TMB).
• To explore TGFB2 as a potential predictive biomarker for immune checkpoint blockade (ICB) therapy in GC.

Main Methods:

• Analysis of TGFB2 expression in GC patient datasets (TCGA-STAD, GEO).
• Gene set enrichment analysis (GSEA) to identify enriched pathways in high/low TGFB2 groups.
• EMT score analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and CIBERSORT analysis for immune cell infiltration.

Main Results:

• Overexpression of TGFB2 correlated with poor prognosis in GC.
• High TGFB2 expression was linked to enriched EMT pathways, while low expression was associated with TMB-related pathways.
• TGFB2 co-expression with neurite pathways suggests a mechanism for EMT induction; T follicular helper cells may mediate TGFB2's effect on TMB.

Conclusions:

• TGFB2 plays a critical role in linking EMT and TMB in gastric cancer (GC).
• TGFB2 negatively correlates with TMB and ICB response across multiple cancer types.
• TGFB2 represents a potential predictive therapeutic target for improving ICB efficacy in GC.