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Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling

Lee, Ju-Seog and Chu, In-Sun and Heo, Jeonghoon and Calvisi, Diego Francesco and Sun, Zongtang and Roskams, Tania and Durnez, Anne and Demetris, Anthony J. and Thorgeirsson, Snorri S. (2004) Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology, Vol. 40 (3), p. 667-676. eISSN 1527-3350. Article.

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DOI: 10.1002/hep.20375

Abstract

We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods. We also identified the genes most strongly associated with survival by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification, suggesting an etiological involvement of these processes in accelerating the progression of HCC. In conclusion, the biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g., HIF1a) for selective treatment of HCC patients.

Item Type:Article
ID Code:1271
Status:Published
Refereed:Yes
Uncontrolled Keywords:Hepatocellular carcinoma, predictive factor, prognostic value, gene expression profiling, patient survival
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Wiley
eISSN:1527-3350
Copyright Holders:© 2004 by the American Association for the Study of Liver Diseases
Additional Information:Pubblicato online il 30 giugno 2004.
Deposited On:18 Aug 2009 10:04

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