Overexpression of YAP1 of EGFR-mutant lung adenocarcinoma before tyrosine kinase inhibitor is associated with poor survival

Abstract

Purpose: EGFR tyrosine kinase inhibitor (EGFR TKI) was approved as a first line treatment for EGFR mutant lung adenocarcinoma (LADC) with advanced stage. YAP1 (Yes-associated protein 1) is a main effector of hippo pathway, related with adverse prognosis and EGFR TKI modulation of non-small cell lung cancer. This study aimed to clarify a prognostic role of YAP1 in EGFR mutant LADC and efficacy for EGFR TKI through the course of EGFR TKI. Materials and Methods: 41 patients with paired lung cancer specimen before and after EGFR TKI were enrolled in this study. The expression of YAP1 protein was evaluated by immunohistochemistry. Results: 15 cases (36.6%) with high YAP1 expression was found in pre-EGFR TKI LADC, while high YAP1 expression in 21 cases (52.5%) was detected after EGFR-TKI. The transitional level of YAP1 between pre- and post-EGFR TKI was significantly upregulated (P=0.002). High YAP1 before EGFR TKI was related with shorter OS (P=0.023) and PFS (P=0.041). In addition, high YAP1 before EGFR TKI in T790M mutant LADC was related with poor OS (P<0.001). Conclusion: YAP1 burden before EGFR TKI was crucial role in prognosis of EGFR mutant LADC treated by EGFR TKI.