TEAD4 Identified as a Potential Biomarker for Gastric Cancer Via Genes Associated with Liquid-Liquid Phase Separation.

[INTRODUCTION] Liquid-liquid phase separation (LLPS) has emerged as a critical mechanism in tumor progression, and its relevance to gastric cancer (GC) is increasingly recognized. However, the mechanisms linking LLPS to GC remain unclear. Preliminary studies suggest that the TEA domain transcription factor 4 (TEAD4) may contribute to tumorigenesis, yet its specific role in GC has not been fully elucidated. This study aims to investigate the potential influence of TEAD4 on GC and to uncover the underlying mechanisms.

[METHODS] TEAD4 was identified as a key gene in GC by intersecting LLPS-related genes with differentially expressed genes from the TCGA-STAD dataset. TEAD4 mRNA and protein expression in GC were analyzed using TCGA, GEO, and HPA databases. Associations with clinical features, diagnostic and prognostic value, immune checkpoints, methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and drug sensitivity were explored. TEAD4 expression was validated in vitro in GC cell lines via RT-qPCR and Western blot. Functional assays were performed by silencing TEAD4 in MKN45 cells to assess its effects on GC cell proliferation, migration, and invasion.

[RESULTS] TEAD4, identified through LLPS-related genes, was found to be abnormally overexpressed in GC at both mRNA and protein levels (P < 0.05). High TEAD4 expression showed strong diagnostic accuracy (AUC > 0.9), correlated with tumor stage and location, and was associated with poorer overall survival (P = 5.02e-05). In GC, low TEAD4 expression was linked to increased immune cell infiltration, higher immune phenotype scores, and elevated expression of immune checkpoints. TEAD4 expression also correlated with methylation status, TMB, MSI, mutational allelic tumor heterogeneity (MATH), and chemosensitivity. In vitro, TEAD4 knockdown reduced proliferation, migration, and invasion of GC cells.

[DISCUSSION] TEAD4 is associated with epigenetic modifications, immune regulation, tumor heterogeneity, and therapeutic response in GC, highlighting its potential mechanistic role in disease progression.

[CONCLUSION] TEAD4 contributes to GC progression and may serve as a biomarker for diagnosis, prognosis, and immune infiltration, providing insights for potential therapeutic strategies.