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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Differential gene expression profiles of hepatocellular carcinomas associated or not with viral infection

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Author(s):
Bellodi-Privato, M. [1] ; Kubrusly, M. S. [1] ; Stefano, J. T. [1] ; Soares, I. C. [2] ; Wakamatsu, A. [2] ; Oliveira, A. C. [1] ; Alves, V. A. F. [2] ; Bacchella, T. [1] ; Machado, M. C. C. [1] ; D'Albuquerque, L. A. C. [1]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Dept Gastroenterol LIM 37 LIM 07, Fac Med, BR-01246903 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Patol LIM 14, Fac Med, BR-01246903 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 42, n. 12, p. 1119-1127, DEC 2009.
Web of Science Citations: 4
Abstract

Chronic hepatitis B (HBV) and C (HCV) virus infections are the most important factors associated with hepatocellular carcinoma (HCC), but tumor prognosis remains poor due to the lack of diagnostic biomarkers. In order to identify novel diagnostic markers and therapeutic targets, the gene expression profile associated with viral and non-viral HCC was assessed in 9 tumor samples by oligo-microarrays. The differentially expressed genes were examined using a z-score and KEGG pathway for the search of ontological biological processes. We selected a non-redundant set of 15 genes with the lowest P value for clustering samples into three groups using the non-supervised algorithm k-means. Fisher's linear discriminant analysis was then applied in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Different transcriptional levels of genes were identified in HCC of different etiologies and from different HCC samples. When comparing HBV-HCC vs HCV-HCC, HBV-HCC/HCV-HCC vs non-viral (NV)-HCC, HBC-HCC vs NV-HCC, and HCV-HCC vs NV-HCC of the 58 non-redundant differentially expressed genes, only 6 genes (IKBK beta, CREBBP, WNT10B, PRDX6, ITGAV, and IFNAR1) were found to be associated with hepatic carcinogenesis. By combining trios, classifiers could be generated, which correctly classified 100% of the samples. This expression profiling may provide a useful tool for research into the pathophysiology of HCC. A detailed understanding of how these distinct genes are involved in molecular pathways is of fundamental importance to the development of effective HCC chemoprevention and treatment. (AU)