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The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma
Transplant Program Administration, Virginia Commonwealth University Health System, 1200 E. Broad St., Richmond, VA 23298, USA
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, 800 E Leigh St., Richmond, VA 23298, USA
Department of Surgery, Virginia Commonwealth University, 1200 E. Broad St., Richmond, VA 23298, USA
* Author to whom correspondence should be addressed.
Received: 23 July 2012; in revised form: 9 August 2012 / Accepted: 13 September 2012 / Published: 18 September 2012
Abstract: Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Patient and disease heterogeneity, differences in statistical methods and multiple testing issues have resulted in a fragmented understanding of the molecular basis of tumor biology. Some researchers have suggested that HCC appears to share pathways with embryonic development. Therefore we generated targeted hypotheses regarding changes in developmental genes specific to the liver in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared to 12 normal livers. Genes specific to non-liver development have known associations with other cancer types but none were expressed in either adult liver or tumor tissue, while 98 of 179 (55%) genes specific to liver development had differential expression between normal and cirrhotic or HCC samples. We found genes from each developmental stage dysregulated in tumors compared to normal and cirrhotic samples. Although there was no single tumor marker, we identified a set of genes (Bone Morphogenetic Protein inhibitors GPC3, GREM1, FSTL3, and FST) in which at least one gene was over-expressed in 100% of the tumor samples. Only five genes were differentially expressed exclusively in late-stage tumors, indicating that while developmental genes appear to play a profound role in cirrhosis and malignant transformation, they play a limited role in late-stage HCC.
Keywords: hepatocellular carcinoma; hepatitis C; microarray analysis
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Behnke, M.; Reimers, M.; Fisher, R. The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma. Cancers 2012, 4, 945-968.
Behnke M, Reimers M, Fisher R. The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma. Cancers. 2012; 4(3):945-968.
Behnke, Martha; Reimers, Mark; Fisher, Robert. 2012. "The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma." Cancers 4, no. 3: 945-968.