High Yes-associated protein 1 with concomitant negative LATS1/2 expression is associated with poor prognosis of advanced gastric cancer

Abstract

The Hippo pathway is a tumour-suppressive pathway and its inactivation is known to be associated with progression and metastasis of various cancers. LATS1/2 (large tumour suppressor homolog 1 and 2), YAP1 (Yes-associated protein 1), and TEAD4 (TEA domain-containing sequence-specific transcription factors 4) are core components of the Hippo pathway, and their prognostic roles have not yet been studied in advanced gastric cancers (AGCs). A total of 318 surgically resected AGCs were retrieved. Immunolabelling for LATS1/2, YAP1 and TEAD4 was compared with clinicopathological factors including patients' survival. High expression of YAP1 and TEAD4 was identified in 108 (34.0%) and 131 (41.2%) cases, respectively, and 223 (70.1%) cases were negative for LATS1/2 expression. High YAP1 expression was significantly correlated with the presence of perineural invasion (p=0.032). High YAP1 and high TEAD4 expressions were significantly associated with poor overall survival (p<0.001 and p=0.003, respectively), and negative LATS1/2 expression was also associated with poor overall survival (p=0.002). Combined expression of YAP1highLATS1/2neg showed the worst overall survival (p<0.001). Expression of YAP1high (HR=2.938; 95% CI 1.726-4.998; p<0.001), LATS1/2neg (HR=0.371; 95% CI 0.181-0.758; p=0.007), and combined YAP1highLATS1/2neg (HR=13.785; 95% CI 3.245-58.554; p<0.001) were independent poor prognostic factors of AGC patients. Combined or individual expression of YAP1, LATS1/2, and TEAD4 can be used as prognostic markers of AGC patients.