Genomic predictors for recurrence patterns of hepatocellular carcinoma: model derivation and validation

Cited 57 time in scopus
Metadata Downloads
Title
Genomic predictors for recurrence patterns of hepatocellular carcinoma: model derivation and validation
Author(s)
J H Kim; B H Sohn; H S Lee; S B Kim; J E Yoo; Y Y Park; W Jeong; S S Lee; E S Park; A Kaseb; B H Kim; W B Kim; J E Yeon; K S Byun; In-Sun Chu; S S Kim; X W Wang; S T Thorgeirsson; J M Luk; K J Kang; J Heo; Y N Park; J S Lee
Bibliographic Citation
PLoS Medicine, vol. 11, no. 12, pp. e1001770-e1001770
Publication Year
2014
Abstract
Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n?=?396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3?3.7; p?=?0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p?=?0.005) but not with late recurrence (p?=?0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1?2.6; p?=?0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus?positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus.Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications.Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification.Please see later in the article for the Editors' Summary.
ISSN
1549-1676
Publisher
Public Library of Science
DOI
http://dx.doi.org/10.1371/journal.pmed.1001770
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
Files in This Item:

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.