Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation

Ji Hoon Kim, Bo Hwa Sohn, Hyun-Sung Lee, Sang-Bae Kim, Jeong Eun Yoo, Yun-Yong Park, Woojin Jeong, Sung Sook Lee, Eun Sung Park, Ahmed Kaseb, Baek Hui Kim, Wan Bae Kim, Jong Eun Yeon, Kwan Soo Byun, In-Sun Chu, Sung Soo Kim, Xin Wei Wang, Snorri S Thorgeirsson, John M Luk, Koo Jeong Kang, Jeonghoon Heo, Young Nyun Park and Ju-Seog Lee

PLOS Medicine, 2014, vol. 11, issue 12, 1-16

Abstract: In this study, Lee and colleagues develop a genomic predictor that can identify patients at high risk for late recurrence of hepatocellular carcinoma (HCC) and provided new biomarkers for risk stratification.Background: 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. Methods and Findings: 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 (

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pmed00:1001770

DOI: 10.1371/journal.pmed.1001770

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