Yes-Associated Protein Is an Independent Prognostic Marker in Hepatocellular Carcinoma

Xu, M. Z., Yao, T. J., Lee, N. P. Y., Ng, I. O. L., Chan, Y. T., Zender, L., Lowe, S. W., Poon, R. T. P., Luk, J. M. (October 2009) Yes-Associated Protein Is an Independent Prognostic Marker in Hepatocellular Carcinoma. Cancer, 115 (19). pp. 4576-4585. ISSN 0008-543X

DOI: 10.1002/cncr.24495


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 =.021]) 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. Cancer 2009;115:4576-85. (C) 2009 American Cancer Society.

Item Type: Paper
Uncontrolled Keywords: hepatocellular carcinoma hippo signaling prognostic marker tumor recurrence Yes-associated protein LIVER-INTESTINE-CADHERIN RISK-FACTORS SIZE-CONTROL HEPATIC RESECTION GROWTH-CONTROL ORGAN SIZE RECURRENCE CANCER YAP IDENTIFICATION
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > cancer types > liver cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Lowe lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date: October 2009
Date Deposited: 19 Feb 2013 15:38
Last Modified: 30 Dec 2014 16:47
PMCID: PMC2811690
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