A Global Risk Score (GRS) to Simultaneously Predict Early and Late Tumor Recurrence Risk after Resection of Hepatocellular Carcinoma

Jeroen Dekervel; Dusan Popovic; Hannah van Malenstein; Petra Windmolders; Line Heylen; Louis Libbrecht; Ashenafi Bulle; Bart De Moor; Eric Van Cutsem; Frederik Nevens; Chris Verslype; Jos van Pelt

doi:10.1016/j.tranon.2016.02.003

A Global Risk Score (GRS) to Simultaneously Predict Early and Late Tumor Recurrence Risk after Resection of Hepatocellular Carcinoma

Transl Oncol. 2016 Apr;9(2):139-146. doi: 10.1016/j.tranon.2016.02.003.

Authors

Affiliations

¹ Laboratory of Hepatology, Department of Clinical and Experimental Medicine, University Hospitals Leuven & KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
² Department of Electrical Engineering (ESAT), STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics/iMinds Medical IT, KU Leuven, Kasteelpark Arenberg 10, 3000, Leuven, Belgium.
³ Department of Nephrology and Renal Transplantation, University Hospitals Leuven & Department of Microbiology and Immunology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
⁴ Laboratory of Hepatology, Department of Clinical and Experimental Medicine, University Hospitals Leuven & KU Leuven, Herestraat 49, 3000, Leuven, Belgium; Department of Pathology, University Hospital Ghent, De Pintelaan 185, 9000, Ghent, Belgium.
⁵ Department of Clinical Digestive Oncology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
⁶ Laboratory of Hepatology, Department of Clinical and Experimental Medicine, University Hospitals Leuven & KU Leuven, Herestraat 49, 3000, Leuven, Belgium; Department of Clinical Digestive Oncology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
⁷ Laboratory of Hepatology, Department of Clinical and Experimental Medicine, University Hospitals Leuven & KU Leuven, Herestraat 49, 3000, Leuven, Belgium. Electronic address: jos.vanpelt@med.kuleuven.be.

Abstract

Objectives: Recurrence of hepatocellular carcinoma can arise from the primary tumor ("early recurrence") or de novo from tumor formation in a cirrhotic environment ("late recurrence"). We aimed to develop one simple gene expression score applicable in both the tumor and the surrounding liver that can predict the recurrence risk.

Methods: We determined differentially expressed genes in a cell model of cancer aggressiveness. These genes were first validated in three large published data sets of hepatocellular carcinoma from which we developed a seven-gene risk score.

Results: The gene score was applied on two independent large patient cohorts. In the first cohort, with only tumor data available, it could predict the recurrence risk at 3 years after resection (68 ± 10% vs 35 ± 7%, P = .03). In the second cohort, when applied on the tumor, this gene score predicted early recurrence (62 ± 5% vs 37 ± 4%, P < .001), and when applied on the surrounding liver tissue, the same genes also correlated with late recurrence. Four patient classes with each different time patterns and rates of recurrence could be identified based on combining tumor and liver scores. In a multivariate Cox regression analysis, our gene score remained significantly associated with recurrence, independent from other important cofactors such as disease stage (P = .007).

Conclusions: We developed a Global Risk Score that is able to simultaneously predict the risk of early recurrence when applied on the tumor itself, as well as the risk of late recurrence when applied on the surrounding liver tissue.