Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma.
BACKGROUND
Yes-associated protein (YAP), a downstream target of the Hippo signaling pathway, was recently linked to hepatocarcinogenesis in a mouse hepatocellular carcinoma (HCC) model. The objective of the current study was to investigate the clinical significance of YAP in HCC and its prognostic values in predicting survival and tumor recurrence.


METHODS
The authors collected 177 pairs of tumor and adjacent nontumor tissue from HCC patients with definitive clinicopathologic and follow-up data. YAP expression was determined by immunohistochemistry, Western blot analysis, and quantitative polymerase chain reaction. Association of YAP with each clinicopathologic feature was analyzed by Pearson chi-square test, and HCC-specific disease-free survival and overall survival by Kaplan-Meier curves and log-rank test. Multivariate Cox regression analyses of YAP in HCC were also performed.


RESULTS
YAP was expressed in the majority of HCC cases (approximately 62%) and mainly accumulated in the tumor nucleus. Overexpression of YAP in HCC was significantly associated with poorer tumor differentiation (Edmonson grade; P = .021) and high serum alpha-fetoprotein (AFP) level (P < .001). Kaplan-Meier and Cox regression data indicated that YAP was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.653; 95% confidence interval [95% CI], 1.081-2.528 [P = .02]) and overall survival (HR, 2.148; 95% CI, 1.255-3.677 [P = .005]).


CONCLUSIONS
YAP is an independent prognostic marker for overall survival and disease-free survival times of HCC patients and clinicopathologically associated with tumor differentiation and serum AFP level. It is a potential therapeutic target for this aggressive malignancy.
Xu
Michelle Z
MZ
Department of Surgery and Center for Cancer Research, the University of Hong Kong, Pokfulam, Hong Kong.
Yao
Tzy-Jyun
TJ
Lee
Nikki P Y
NP
Ng
Irene O L
IO
Chan
Yuk-Tat
YT
Zender
Lars
L
Lowe
Scott W
SW
Poon
Ronnie T P
RT
Luk
John M
JM
D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000401:mortality; D018797:Cell Cycle Proteins; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D016019:Survival Analysis; D014157:Transcription Factors / Q000032:analysis*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human