Collectively, our results indicate that: (i) a subset of GC is characterized by a signature denoting deregulation of both Hippo and Wnt, (ii) the coexistence of nuclear TAZ expression and pathogenic Wnt pathway mutations seems to be predictive of shorter PFS, and then reduced efficacy of first-line chemotherapy, and (iii) the TAZpos/WNTmut signature may also represent an adverse prognostic factor. The gene discussed is WWTR1; the disease is gastric cancer.