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


CONCLUSIONS
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.
De Giorgi
Valeria
V
Molecular Biology and Viral Oncogenesis & AIDS Refer, Center, Ist, Naz, Tumori Fond, G Pascale, Naples, Italy. valeriadegiorgi@tin.it
Monaco
Alessandro
A
Worchech
Andrea
A
Tornesello
Marialina
M
Izzo
Francesco
F
Buonaguro
Luigi
L
Marincola
Francesco M
FM
Wang
Ena
E
Buonaguro
Franco M
FM
D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000502:physiology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis
D015415:Biomarkers