Cytoplasmic YAP expression is associated with prolonged survival in patients with lung adenocarcinomas and epidermal growth factor receptor tyrosine kinase inhibitor treatment.
BACKGROUND
Yes-associated protein (YAP) has been reported to be associated with the prognosis of various cancers and also to affect epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) activity in ovarian cancer cell lines. However, few studies have evaluated YAP protein expression in lung cancer, and the results have lacked consistency.


METHODS
YAP expression was evaluated in a total of 205 curatively resected lung adenocarcinomas and 36 cases of EGFR-mutated TKI-treated patients. Correlations between the expression of YAP and clinicopathologic features, response to EGFR-TKI treatment, and prognostic significance were analyzed.


RESULTS
High cytoplasmic YAP expression was positively correlated with the clinicopathologic parameters that have been associated with favorable prognosis. Multivariate analysis revealed that high cytoplasmic YAP expression was an independent prognostic factor in lung adenocarcinomas (progression-free survival: hazard ratio [HR] 0.659; 95 % confidence interval [CI] 0.431-1.010; p = 0.050; overall survival: HR, 0.474; 95 % CI 0.263-0.854; p = 0.013) and EGFR-TKI-treated patients with EGFR mutation (progression-free survival: HR, 0.346; 95 % CI 0.146-0.818; p = 0.016; overall survival: HR, 0.291; 95 % CI 0.125-0.676; p = 0.004).


CONCLUSIONS
High cytoplasmic YAP expression predicted a good clinical outcome for patients with lung adenocarcinoma and in EGFR-TKI-treated patients. Therefore, YAP may play a role in EGFR-TKI-treated lung cancer, and YAP targeting may enhance therapeutic effects in combination with other cancer drugs.
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
Ping-Li
PL
Sun
Ji Eun
JE
Kim
Seol Bong
SB
Yoo
Hyojin
H
Kim
Yan
Y
Jin
Sanghoon
S
Jheon
Kwhanmien
K
Kim
Choon Taek
CT
Lee
Jin-Haeng
JH
Chung
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis* / Q000235:genetics; D000230:Adenocarcinoma / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003593:Cytoplasm / Q000737:chemistry; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics; D011013:Pneumonectomy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib