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Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation
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نویسنده
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kim j.h. ,sohn b.h. ,lee h.-s. ,kim s.-b. ,yoo j.e. ,park y.-y. ,jeong w. ,lee s.s. ,park e.s. ,kaseb a. ,kim b.h. ,kim w.b. ,yeon j.e. ,byun k.s. ,chu i.-s. ,kim s.s. ,wang x.w. ,thorgeirsson s.s. ,luk j.m. ,kang k.j. ,heo j. ,park y.n. ,lee j.-s.
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منبع
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plos medicine - 2014 - دوره : 11 - شماره : 12
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چکیده
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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. © 2014 kim et al.
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آدرس
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department of systems biology,division of cancer medicine,the university of texas md anderson cancer center,houston,tx,united states,kleberg center for molecular markers,division of cancer medicine,the university of texas md anderson cancer center,houston,tx,united states,division of gastroenterology and hepatology,department of internal medicine university college of medicine,seoul, South Korea, department of systems biology,division of cancer medicine,the university of texas md anderson cancer center,houston,tx,united states,kleberg center for molecular markers,division of cancer medicine,the university of texas md anderson cancer center,houston,tx, United States, department of systems biology,division of cancer medicine,the university of texas md anderson cancer center,houston,tx,united states,kleberg center for molecular markers,division of cancer medicine,the university of texas md anderson cancer center,houston,tx, United States, department of systems biology,division of cancer medicine,the university of texas md anderson cancer center,houston,tx,united states,kleberg center for molecular markers,division of cancer medicine,the university of texas md anderson cancer center,houston,tx, United States, department of pathology and brain korea 21 project for medical science,yonsei university college of medicine,seoul, South Korea, asan institute for life sciences,asan medical center,department of medicine,university of ulsan college of medicine,seoul, South Korea, department of life sciences,division of life and pharmaceutical sciences,center for cell signaling and drug discovery research,ewha womans university,seoul, South Korea, department of hematology-oncology,inje university haeundae paik hospital,busan, South Korea, institute for medical convergence,yonsei university college of medicine,seoul, South Korea, department of gi medical oncology,division of cancer medicine,the university of texas md anderson cancer center,houston,tx, United States, department of pathology,department of internal medicine university college of medicine,seoul, South Korea, department of surgery,department of internal medicine university college of medicine,seoul, South Korea, division of gastroenterology and hepatology,department of internal medicine university college of medicine,seoul, South Korea, division of gastroenterology and hepatology,department of internal medicine university college of medicine,seoul, South Korea, korean bioinformation center research institute of bioscience and biotechnology,daejeon, South Korea, department of biochemistry and molecular biology,medical research center and biomedical science institute,school of medicine,kyung hee university,seoul, South Korea, laboratory of human carcinogenesis,national cancer institute,national institutes of health,bethesda,md, United States, laboratory of experimental carcinogenesis,national cancer institute,national institutes of health,bethesda,md, United States, department of pharmacology,national university of singapore, Singapore, department of surgery,keimyung university school of medicine,daegu, South Korea, departments of molecular biology and immunology,kosin university college of medicine,busan, South Korea, department of pathology and brain korea 21 project for medical science,yonsei university college of medicine,seoul, South Korea, department of systems biology,division of cancer medicine,the university of texas md anderson cancer center,houston,tx,united states,kleberg center for molecular markers,division of cancer medicine,the university of texas md anderson cancer center,houston,tx,united states,department of biochemistry and molecular biology,medical research center and biomedical science institute,school of medicine,kyung hee university,seoul, South Korea
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Authors
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