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Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma

Title
Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma
Authors
Sohn, Bo HwaShim, Jae-JunKim, Sang-BaeJang, Kyu YunKim, Soo MiKim, Ji HoonHwang, Jun EulJang, Hee-JinLee, Hyun-SungKim, Sang-CheolJeong, WoojinKim, Sung SooPark, Eun SungHeo, JeonghoonKim, Yoon JunKim, Dae-GhonLeem, Sun-HeeKaseb, AhmedHassan, Manal M.Cha, MinseChu, In-SunJohnson, Randy L.Park, Yun-YongLee, Ju-Seog
Ewha Authors
정우진
SCOPUS Author ID
정우진scopus
Issue Date
2016
Journal Title
CLINICAL CANCER RESEARCH
ISSN
1078-0432JCR Link1557-3265JCR Link
Citation
vol. 22, no. 5, pp. 1256 - 1264
Publisher
AMER ASSOC CANCER RESEARCH
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Purpose: The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. Experimental Design: We analyzed gene expression data from Mst1/2(-/-) and Sav1(-/-) mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. Results: HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P < 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12-2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P < 0.001). Conclusions: Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. Clin Cancer Res; 22(5); 1256-64. (C) 2015 AACR.
DOI
10.1158/1078-0432.CCR-15-1447
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자연과학대학 > 생명과학전공 > Journal papers
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