journal contribution
posted on 2023-03-31, 18:27 authored by Bo Hwa Sohn, Jae-Jun Shim, Sang-Bae Kim, Kyu Yun Jang, Soo Mi Kim, Ji Hoon Kim, Jun Eul Hwang, Hee-Jin Jang, Hyun-Sung Lee, Sang-Cheol Kim, Woojin Jeong, Sung Soo Kim, Eun Sung Park, Jeonghoon Heo, Yoon Jun Kim, Dae-Ghon Kim, Sun-Hee Leem, Ahmed Kaseb, Manal M. Hassan, Minse Cha, In-Sun Chu, Randy L. Johnson, Yun-Yong Park, Ju-Seog Lee Figure S1: Significant concordance between silence of Hippo signature and YAP1 expression in human hepatocellular carcinoma (HCC); Figure S2: Venn diagram of gene lists from two different gene expression signatures; Table S1: Genes in the SOH signature; Table S2: Functional categories of genes in the SOH signature; Table S3: Canonical Pathways enriched in the SOH signature; Table S4: Significant association between the SOH subtype and YAP1 protein expression in HCC; Table S5: Univariate and multivariate Cox regression analyses of recurrence-free survival with continuous SOH probability; Table S6: Univariate and multivariate Cox regression analyses of overall survival; Table S7: Univariate and multivariate Cox regression analyses of overall survival with continuous SOH probability; Table S8: Drop in concordance index in multivariable analysis; Table S9: Concordance of silence of Hippo signature with other prognostic HCC gene expression signatures in the NCI cohort; Table S10: Characteristics of HCC patients in the MSH cohort, stratified by SOH signature.
Funding
the 2011 and 2012 cycles of the MD Anderson Sister Institute Network Fund
Scientific Research Center Program
Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education
GlaxoSmithKline Research Fund of the Korean Association
History
ARTICLE 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. ©2015 AACR.
