Abstract
The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) remains controversial. To understand the transition from benign to malignant, we studied the gene expression patterns in liver tissues at different stages, including normal, cirrhosis, and different HCC stages. We studied 108 liver tissue samples obtained from 88 distinct patients (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and 47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of high-density oligonucleotide arrays. Among probe sets identified as differentially expressed via the F test, all pairwise comparisons were performed. Cirrhotic tissues with and without concomitant HCC were further evaluated, and a classifier was used to predict whether the tissue type was associated with HCC. Differential expression profiles were analyzed using Interaction Networks and Functional Analysis. Characteristic gene signatures were identified when normal tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with HCC. Pathway analysis classified the cellular and biological functions of the DEG as related to cellular growth and proliferation, cell death and inflammatory disease in cirrhosis; cell death, cell cycle, DNA replication, and immune response in early HCCs; and cell death, cell growth and proliferation, cell cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were identified at different stages of HCV-HCC progression. A set of genes were identified to predict whether the cirrhotic tissue was associated with HCC.
Highlights
According to the most recently available worldwide estimates, liver cancer is the sixth leading cancer type, with 626,162 cases estimated in 2002, and is the third leading cause of cancer death, with an estimated 598,321 deaths that same year [1]
From the analysis of the 17 unique probe sets (n = 16 genes) differentially expressed in hepatitis C virus (HCV)-hepatocellular carcinoma (HCC) samples when compared with HCV cirrhotic tissues from patients with HCC (Supplemental Table 2), genes involved in regulation of transcription (TAF10) and DNA repair (APEX2) were upregulated in HCVHCC samples, whereas coagulation factors (F5, tissue factor pathway inhibitor (TFPI)) and apoptosis genes (BAG5) were downregulated
From the analysis of the resulting 878 probe sets (Figure 1A) we identified genes related to cell division (CDC2L6, CDKN1C, CDCA4), cell adhesion (CDH22, cadherin 4 (CDH4), CDH6), apoptosis (TNFAIP3, TNFRSF21, MCL1, BNIP1, BAK1) being differentially expressed in HCV-HCC tissue samples compared with HCV cirrhotic tissues
Summary
According to the most recently available worldwide estimates, liver cancer is the sixth leading cancer type, with 626,162 cases estimated in 2002, and is the third leading cause of cancer death, with an estimated 598,321 deaths that same year (http://www-dep.iarc.fr/) [1]. The incidence of hepatocellular carcinoma (HCC) in the US is increasing because of the increased prevalence of hepatitis C virus (HCV) infection [2,3,4]. Surgical resection and liver transplantation are still the only potentially curative treatments for HCC [5,6,7]. The major risk factors for HCC development are well defined, and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years [16,17]. An association between HCV infection and later development of HCC has been established, currently the actual mechanisms that lead to malignant transformation are largely unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
