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Cited by 528Hippo pathway signaling and YAP/TAZHepatocellular Carcinoma Treatment and PrognosisCancer-related molecular mechanisms research

Yes‐associated protein is an independent prognostic marker in hepatocellular carcinoma

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Xu, Michelle Z., Yao, Tzy‐Jyun, Lee, Nikki P. Y., Ng, Irene O. L., Chan, Yuk‐Tat, Zender, Lars, Lowe, Scott W., Poon, Ronnie T. P. +1 more·2009·Cancer
DOI 10.1002/cncr.24495PMC PMC2811690
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Abstract

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 α‐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. Cancer 2009. © 2009 American Cancer Society.

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Cited by

Sorted by citations

Authors
Xu, M. Z., Yao, T., Lee, N. P. Y., Ng, I. O. L., Chan, Y., Zender, L., Lowe, S. W., Poon, R. T. P., & Luk, J. M.
Affiliations
  • University of Hong Kong (HK)
  • Howard Hughes Medical Institute (US)
ORCID
Venue
Cancer
Publisher
Wiley
Published
2009-06-23
Volume
115
Issue
19
Pages
4576-4585
ISSN
  • 0008-543X (ISSN-L)
  • 1097-0142
DOI
10.1002/cncr.24495
PMC
PMC2811690
OpenAlex
W2132256680
Cited by
528
References
1
Citations by year
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FWCI
12.32
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Funders
National Cancer Institute (P01CA013106, P30CA008748)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
YAP, hepatocellular carcinoma, prognostic factors, Hippo signaling pathway, disease-free survival, overall survival, tumor recurrence, tumor differentiation, alpha-fetoprotein, therapeutic target
MeSH terms
Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Nuclear Proteins, Prognosis, Transcription Factors, Biomarkers, Tumor, Survival Analysis, Cell Cycle Proteins

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