Expression of the Hippo transducer TAZ in association with WNT pathway mutations impacts survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy

摘要: An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization GC demonstrated pathway is targeted by mutations. On this ground, we hypothesized YAP/TAZ- Wnt-related biomarkers may predict clinical outcomes patients treated with chemotherapy. In present study, included 86 advanced first-line chemotherapy prospective phase II trials or routine practice. Tissue samples were immunostained to evaluate expression YAP/TAZ. Mutational status key genes (CTNNB1, APC FBXW7) was assessed DNA next-generation sequencing (NGS). Survival curves estimated compared Kaplan–Meier product-limit method log-rank test, respectively. Variables potentially affecting progression-free survival (PFS) verified univariate Cox proportional hazard models. The final multivariate models obtained variables testing significant at analysis, adjusting for all plausible predictors outcome interest (PFS). We observed association between TAZ mutations (Chi-squared p = 0.008). Combined (TAZpos/WNTmut) more frequently shortest (negative outliers) (Fisher p = 0.021). Uni-and regression analyses whose tumors harbored TAZpos/WNTmut signature had an increased risk disease progression (univariate Cox: HR 2.27, 95% CI 1.27–4.05, p = 0.006; 2.73, 1.41–5.29, p = 0.003). Finally, negatively impacted overall survival. Collectively, our findings indicate YAP/TAZ–Wnt be active GC, conferring chemoresistant traits translate into adverse outcomes.