Clinical—Liver, Pancreas, and Biliary TractCombining Clinical, Pathology, and Gene Expression Data to Predict Recurrence of Hepatocellular Carcinoma
Section snippets
Patients and Genomic Profiling
We included 287 HCC patients treated with surgical resection in 4 institutions, 3 from the HCC Genomic Consortium: Mount Sinai School of Medicine in New York (n = 93), Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Tumori in Milan (n = 82), Hospital Clinic in Barcelona (n = 50), and the Toranomon Hospital in Tokyo (n = 62). All study protocols previously were approved by their respective Institutional Review Boards.6, 10 Sample processing, RNA extraction, and
Genomic Landscape of Early HCC
Among the 22 signatures evaluated, 17 (ie, 15 from the tumor and 2 from the adjacent nontumoral cirrhotic tissue) were able to confidently allocate patients (FDR < 0.05) within their predicted poor outcome subclass, as opposed to the remaining 5 signatures (Table 1). Figure 2 summarizes the prediction obtained for each of the 287 patients. The proliferation signature10 was the most prevalent prediction in our dataset (39%; 112 of 287), whereas the signature of metastatic HCC24 was identified in
Discussion
Accurate prognosis prediction is crucial in modern oncology. In HCC, clinical-based staging algorithms (eg, BCLC) provide a useful framework for decision making.32 This study introduces an integrated prognostic model combining genomic and clinicopathologic data to improve outcome prediction in patients with single-nodule early HCC. In addition, we show that genomic profiles of both the tumor and the adjacent tissue are complementary in refining the prognosis of individuals undergoing surgical
References (41)
- et al.
Hepatocellular carcinoma
Lancet
(2003) - et al.
Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy
J Hepatol
(2003) - et al.
Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study
Lancet Oncol
(2009) - et al.
Relation between resistance of Philadelphia-chromosome-positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor STI571 and gene-expression profiles: a gene-expression study
Lancet
(2002) - et al.
Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment
Cancer Cell
(2006) - et al.
Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer
Cancer Cell
(2008) - et al.
Consistency of random survival forests
Stat Prob Lett
(2010) - et al.
Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis
Lancet Oncol
(2009) - et al.
Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection
Lancet
(2003) - et al.
Molecular-based prediction of early recurrence in hepatocellular carcinoma
J Hepatol
(2004)
Molecular prediction of early recurrence after resection of hepatocellular carcinoma
Eur J Cancer
Cancer statistics, 2009
CA Cancer J Clin
Resection and liver transplantation for hepatocellular carcinoma
Semin Liver Dis
Design and endpoints of clinical trials in hepatocellular carcinoma
J Natl Cancer Inst
Gene expression in fixed tissues and outcome in hepatocellular carcinoma
N Engl J Med
Enabling personalized cancer medicine through analysis of gene-expression patterns
Nature
Focal gains of VEGFA and molecular classification of hepatocellular carcinoma
Cancer Res
Progenitor-derived hepatocellular carcinoma model in the rat
Hepatology
Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets
Hepatology
Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin
Hepatology
Cited by (357)
GCF2 mediates nicotine-induced cancer stemness and progression in hepatocellular carcinoma
2024, Ecotoxicology and Environmental SafetyMRPL21 promotes HCC proliferation through TP53 mutation-induced apoptotic resistance
2024, Tissue and CellCellular and Molecular Techniques
2023, MacSween's Pathology of the Liver, Eighth EditionTransplantation Pathology
2023, MacSween's Pathology of the Liver, Eighth EditionImmune index: A gene and cell prognostic signature for immunotherapy response prediction in hepatocellular carcinoma
2023, Pharmacological Research
Conflicts of interest The authors disclose no conflicts.
Funding Augusto Villanueva is a recipient of a Sheila Sherlock fellowship (European Association for the Study of the Liver); Clara Alsinet is supported by a grant from the Instituto de Salud Carlos III (ISCIII/FIS FI09/00605); Helena Cornella is supported by a grant from the Spanish National Health Institute (SAF-2007-61898); Arthur Liberzon is supported by a grant from the US National Institutes of Health (5R01CA121941); Jordi Bruix is supported by a grant from the Instituto de Salud Carlos III (ISCIII/FIS PI 05-0150); and Josep Llovet is supported by grants from the US National Institutes of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01), European Commission-FP7 Framework (HEPTROMIC, proposal no: 259744), the Samuel Waxman Cancer Research Foundation and the Spanish National Health Institute (SAF-2007-61898 and SAF-2010-16055). The study was supported by the Landon Foundation-American Association for Cancer Research Innovator Award for International Collaboration in Cancer Research.