The incidence of hepatocellular carcinoma (HCC) is rising in the USA because of the increased prevalence of cirrhosis from HCV infection. Surgical resection (SR) and liver transplantation (LT) still represent the only potentially curative treatments. Since 80% of HCC patients in the USA have cirrhosis, optimum care requires the analysis of cancer stage to predict recurrence, and the determination of liver reserve to predict suitability of SR vs. LT to prevent death from liver failure. LT is limited by the shortage of organs, with up to 30% of patients developing contraindications to the procedure while waiting for a donor. Living Donor Liver Transplant (LDLT) is one way to shorten the waiting time. Accurate tumor staging in patients with HCC is critical to provide a potentially curative treatment. Molecular markers for HCC metastasis and recurrence could provide additional information to that gained from traditional clinical and histopathological. features. We will explore the hypothesis that establishment of a molecular-based method for the classification of HCV- HCC at diagnosis will permit the detection of distinct subgroups of HCC patients with different prognoses,- allowing greater accuracy in the selection of patients for treatment cure with transplantation. In this multi- enter prospective project, nested within the A2ALL NIH-NIDDK Cohort Study, gene expression profiling and genome-wide LOH analysis will be used for the studies. We propose: 1- To study HCV-HCC initiation (comparing gene expression profiles and LOH patterns in HCV infected patients with and without HCC awaiting LT) and to identify a set of significant genes for classifying high-risk patients with a potential for developing HCC;2-To analyze disease progression, establishing a molecular fingerprint for distinguishing HCV-HCC patients awaiting a donor with the greatest risk for developing HCC recurrence;3-The molecular j'ngerprint established in aim 2 will be studied for it's accuracy to predict outcomes post-LT by performing survival analysis and comparing the risk of post-LT HCC recurrence stratified by LDLT and Deceased Donor .iver Transplant recipient groups. We propose that establishment of a molecular-based method for the classification of HCV-HCC at diagnosis II permit the detection of distinct subgroups of HCC patients with different prognoses, allowing greater accuracy in selection of patients for treatment cure with transplantation.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Epidemiology of Cancer Study Section (EPIC)
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Doo, Edward
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Virginia Commonwealth University
Schools of Medicine
United States
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Ramanathan, Rajesh; Sharma, Amit; Lee, David D et al. (2014) Multimodality therapy and liver transplantation for hepatocellular carcinoma: a 14-year prospective analysis of outcomes. Transplantation 98:100-6
Behnke, Martha K; Reimers, Mark; Fisher, Robert A (2013) Stem cell and hepatocyte proliferation in hepatitis C cirrhosis and hepatocellular carcinoma: transplant implications. Ann Hepatol 13:45-53
Behnke, Martha; Reimers, Mark; Fisher, Robert (2012) The expression of embryonic liver development genes in hepatitis C induced cirrhosis and hepatocellular carcinoma. Cancers (Basel) 4:945-68
Archer, Kellie J; Mas, Valeria R; Maluf, Daniel G et al. (2010) High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma. Mol Genet Genomics 283:341-9
Archer, Kellie J; Zhao, Zhongming; Guennel, Tobias et al. (2010) Identifying genes progressively silenced in preneoplastic and neoplastic liver tissues. Int J Comput Biol Drug Des 3:52-67
Archer, Kellie J; Mas, Valeria R; David, Krystle et al. (2009) Identifying genes for establishing a multigenic test for hepatocellular carcinoma surveillance in hepatitis C virus-positive cirrhotic patients. Cancer Epidemiol Biomarkers Prev 18:2929-32
Mas, Valeria R; Maluf, Daniel G; Archer, Kellie J et al. (2009) Proteomic analysis of HCV cirrhosis and HCV-induced HCC: identifying biomarkers for monitoring HCV-cirrhotic patients awaiting liver transplantation. Transplantation 87:143-52
Archer, Kellie J; Mas, Valeria R; O'Brien, Thomas R et al. (2009) Quality assessment of microarray data in a multicenter study. Diagn Mol Pathol 18:34-43
Mas, Valeria R; Maluf, Daniel G; Archer, Kellie J et al. (2009) Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol Med 15:85-94
Archer, K J; Mas, V R (2009) Ordinal response prediction using bootstrap aggregation, with application to a high-throughput methylation data set. Stat Med 28:3597-610

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