Epigallocatechin gallate is associated with PDGFRB downregulation and altered PI3K-AKT signaling in gastric cancer.
BACKGROUND: Gastric cancer (GC) remains a major cause of cancer-related mortality worldwide. Epigallocatechin gallate (EGCG), a natural polyphenol derived from green tea, exhibits anticancer properties; however, its molecular targets and regulatory mechanisms in GC are not fully elucidated. This study aimed to identify candidate EGCG-associated genes in GC and generate a hypothesis for future mechanistic investigation. METHODS: Differentially expressed genes (DEGs) in GC were identified and intersected with EGCG-associated targets retrieved from The Cancer Genome Atlas (TCGA) and GeneCards public databases. Least absolute shrinkage and selection operator (LASSO) regression and Cox proportional hazards analyses were performed to screen prognostically relevant genes. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves. Functional enrichment analysis was conducted to explore biological significance. Public single-cell RNA sequencing datasets were analyzed to determine the cellular localization of platelet-derived growth factor receptor beta (PDGFRB), while DepMap transcriptomic data were used to assess its expression across GC cell lines. In vitro assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell migration, and Western blotting, were performed to evaluate the biological effects of EGCG on GC-associated signaling pathways. RESULTS: Thirty-eight EGCG-associated DEGs were identified. Enrichment analysis revealed these genes were involved in cancer-associated pathways. LASSO-Cox modelling identified four candidate genes. Among them, PDGFRB was selected for further investigation based on its prognostic relevance and favorable diagnostic performance. PDGFRB expression was significantly higher in the TCGA genomically stable (GS) subtype than in the other molecular subtypes and was predominantly localized to cancer-associated fibroblasts (CAFs) and pericytes in single-cell RNA sequencing analysis. DepMap data demonstrated heterogeneous PDGFRB expression across GC cell lines. In vitro experiments showed that EGCG inhibited proliferation, migration, and invasion, reduced PDGFRB protein expression, and was associated with apoptosis-related protein changes and altered PI3K-AKT signaling. CONCLUSIONS: Our findings suggest that EGCG treatment was associated with reduced PDGFRB expression and altered PI3K-AKT signaling in GC cells. These findings identify PDGFRB as a candidate EGCG-associated gene and provide a hypothesis for future mechanistic investigation.