Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

doi:10.1186/1479-5876-7-85

Journal of Translational Medicine

Volume 7

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De Giorgi V
Monaco A
Worchech A
Tornesello ML
Izzo F
Buonaguro L
Marincola FM
Wang E
Buonaguro FM

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De Giorgi V
Monaco A
Worchech A
Tornesello ML
Izzo F
Buonaguro L
Marincola FM
Wang E
Buonaguro FM
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Research

Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

Valeria De Giorgi¹^,2 , Alessandro Monaco³ , Andrea Worchech³^,4^,5 , MariaLina Tornesello¹ , Francesco Izzo⁶ , Luigi Buonaguro¹ , Francesco M Marincola³ , Ena Wang³ and Franco M Buonaguro¹

¹Molecular Biology and Viral Oncogenesis & AIDS Refer. Center, Ist. Naz. Tumori "Fond. G. Pascale", Naples - Italy

²Department of Chemistry, University of Naples "Federico II", Naples, Italy

³Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD -USA

⁴Genelux Corporation, Research and Development, San Diego Science Center, San Diego, CA, USA

⁵Department of Biochemistry, Biocenter, University of Wuerzburg, Am Hubland, Wuerzburg, Germany

⁶Div. of Surgery "D", Ist. Naz. Tumori "Fond. G. Pascale", Naples - Italy

author email corresponding author email

Journal of Translational Medicine 2009, 7:85doi:10.1186/1479-5876-7-85


Published:	12 October 2009

Abstract

Background

Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls.

Methods

Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of t-test was set at 0.001.

Results

Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart.

Conclusion

In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection, diagnosis, and classification of HCV-related HCC.