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Title 

Inactivation of hippo pathway is significantly associated with poor prognosis in hepatocellular carcinoma

Authors 

B H SohnJ J ShimS B KimK Y JangS M KimJ H KimJ E HwangH J JangH S LeeS C KimW JeongS S KimE S ParkJ JeoY J KimD G KimS H LeemA KasebM M HassanM ChaIn-Sun ChuR L JohnsonY Y ParkJ S Lee

Publisher 

American Association for Cancer Research

Issue Date 

2016

Citation 

Clinical Cancer Research, vol. 22, no. 5, pp. 1256-1264

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.

ISSN 

1078-0432

Link 

http://dx.doi.org/10.1158/1078-0432.CCR-15-1447

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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