TY - JOUR
T1 - Gene-expression signature of vascular invasion in hepatocellular carcinoma
AU - Mínguez, Beatriz
AU - Hoshida, Yujin
AU - Villanueva, Augusto
AU - Toffanin, Sara
AU - Cabellos, Laia
AU - Thung, Swan
AU - Mandeli, John
AU - Sia, Daniela
AU - April, Craig
AU - Fan, Jian Bing
AU - Lachenmayer, Anja
AU - Savic, Radoslav
AU - Roayaie, Sasan
AU - Mazzaferro, Vincenzo
AU - Bruix, Jordi
AU - Schwartz, Myron
AU - Friedman, Scott L.
AU - Llovet, Josep M.
N1 - Funding Information:
Beatriz Mínguez was the recipient of a grant from Programa de Estancias de Movilidad Postdoctoral en el Extranjero incluidas las ayudas MICINN/Fulbright (EX 2008-0632), Augusto Villanueva was supported by a Sheila Sherlock Fellowship, Sara Toffanin and Vincenzo Mazzaferro were supported by Italian National Ministry of Health and the Italian Association of Cancer Research. Anja Lachenmayer was supported by a postdoctoral fellowship from German Research Foundation. BCLC was supported by the Spanish Biomedical Research Network (CIBER) for the area of hepatic and digestive disorders and by a grant of the Instituto de Salud Carlos III (PI 08/0146). Scott Friedman was supported by grants from NIDDK, RO1-37340 and RO1-56621. Josep M. Llovet is supported by grants from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (J.M.L.: 1R01DK076986–01), European Comission-FP7 grant (HEPTROMIC; Proposal No: 259744-2;), The Samuel Waxman Cancer Research Foundation and the Spanish National Health Institute (SAF-2007-61898; SAF2010-16055). The study was supported by the Landon Foundation – American Association for Cancer Research Innovator Award for International Collaboration in Cancer Research-2009.
PY - 2011/12
Y1 - 2011/12
N2 - Background & Aims: Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30-40% of patients with early tumors, remains elusive. Methods: A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. Results: A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48-7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17-6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). Conclusions: The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.
AB - Background & Aims: Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30-40% of patients with early tumors, remains elusive. Methods: A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. Results: A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48-7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17-6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). Conclusions: The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.
KW - Diagnosis
KW - Gene-expression signature
KW - Hepatocellular carcinoma
KW - Liver transplantation
KW - Prediction
KW - Surgical resection
KW - Vascular invasion
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U2 - 10.1016/j.jhep.2011.02.034
DO - 10.1016/j.jhep.2011.02.034
M3 - Article
C2 - 21703203
AN - SCOPUS:80054717602
SN - 0168-8278
VL - 55
SP - 1325
EP - 1331
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 6
ER -