Prognostic significance of co-expression of c-MET and EGFR in locally advanced and metastatic gastric cancer: a retrospective cohort study

Objective Gastric cancer (GC) remains a leading cause of cancer-related mortality globally. While molecular targeted therapies against HER2 and PD-L1 have advanced, the role of receptor tyrosine kinase (RTK) co-activation, specifically between c-MET and EGFR, remains elusive in GC. This study aimed to investigate the correlation between c-MET and EGFR overexpression and clinicopathological features and prognosis in patients with gastric cancer, and to reveal prognostic significance of co-expression of c-MET and EGFR in gastric adenocarcinoma. Methods The clinicopathological data of 214 Chinese patients with GC were retrospectively analyzed, and the expression level of c-MET and EGFR were detected by immunohistochemistry. χ 2 test was used to investigate associations with clinicopathological features. Kaplan-Meier survival curve and Cox proportional hazards models were employed to analyze the relationship between c-MET, EGFR and co-expression and patient prognosis. Results The positive expression rates for c-MET and EGFR were 21.96% (47/214) and 68.22% (146/214), respectively. c-MET overexpression was significantly served as an independent predictor of poor OS ( P=0.023 ). Conversely, EGFR expression alone showed no significant prognostic value. Notably, 18.22% (39/214) of cases exhibited co-expression of c-MET and EGFR. Patients with isolated EGFR expression exhibited the most favorable prognosis, while the isolated c-MET expression group had the worst clinical survival. Moreover, patients with c-MET and EGFR co-expression achieved better survival than those with isolated c-MET expression ( P = 0.007 ). Conclusion c-MET overexpression is a robust prognostic indicator of adverse outcomes in GC. The frequent co-expression of c-MET and EGFR suggests a potential mechanism of RTK cross-talk, warranting further investigation into dual-targeted therapeutic strategies.