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HPB Surgery  2012 

Neither MICA Nor DEPDC5 Genetic Polymorphisms Correlate with Hepatocellular Carcinoma Recurrence following Hepatectomy

DOI: 10.1155/2012/185496

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Abstract:

Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7% in MICA GG allele carriers, 38.7% in GA, and 20.8% in AA, respectively ( ). The five-year RFS rate was 23.8% in DEPDC5 TT allele carriers and 31.8% in TG/GG, respectively ( ). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers ( ). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages. 1. Introduction Hepatocellular carcinoma (HCC) is among the top five causes of cancer-related death worldwide [1] and is ranked third in the leading cause of death from cancer in Japanese men, of which approximately 70% is related with hepatitis C virus (HCV) infection [2]. Despite the recent development of cancer therapies, such as surgical resection, liver transplantation, local ablation, arterial embolization, and tyrosine kinase inhibitors, almost 70% of patients will relapse within 5 years after initial surgical resection [3]. In particular, a significant association between the histological hepatitis states of the remnant livers and HCC recurrence has been reported. High histological hepatitis activity and high serum levels of transaminase are related to a high recurrence rate, especially in HCV patients. This recurrence is presumed to be caused by multicentric occurrence of HCC after hepatectomy in patients with HCV [4, 5]. Recent technical developments in genome sequencing have enabled genome-wide association studies, which clarified that two single nucleotide polymorphisms (SNPs) are associated with progression to HCC among HCV patients. The SNPs are in the MICA [6] and DEPDC5 genes [7]. The MICA gene encodes a major histocompatibility

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