Yuji Hodo1, Masao Honda, Akihiro Tanaka, Yoshimoto Nomura, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Akito Sakai, Motoko Sasaki, Yasuni Nakanuma, Mitsuhiko Moriyama, Shuichi Kaneko.
Abstract
PURPOSE: Several single-nucleotide polymorphisms (SNP) in the interleukin-28B (IL-28B) locus have recently been shown to be associated with antiviral treatment efficacy for chronic hepatitis C (CHC). However, such an association with hepatocellular carcinoma (HCC) is unkno3 we investigated the association between the IL-28B genotype and the biology and clinical outcome of patients with HCC receiving curative treatment. EXPERIMENTAL
DESIGN: Genotyping of 183 patients with HCC with CHC who were treated with hepatic resection or radiofrequency ablation (RFA) was carried out, and the results were analyzed to determine the association between the IL-28B genotype (rs8099917) and clinical outcome. Gene expression profiles of 20 patients with HCC and another series of 91 patients with CHC were analyzed using microarray analysis and gene set enrichment analysis. Histologic and immunohistochemical analyses were also conducted.
RESULTS: The TT, TG, and GG proportions of the rs8099917 genotype were 67.8% (124 of 183), 30.6% (56 of 183), and 1.6% (3 of 183), respectively. Multivariate Cox proportional hazard analysis showed that the IL-28B TT genotype was significantly associated with HCC recurrence (P = 0.007; HR, 2.674; 95% confidence interval, 1.16-2.63). Microarray analysis showed high expression levels of IFN-stimulated genes in background liver samples and immune-related genes in tumor tissues of the IL-28B TG/GG genotype. Histologic findings showed that more lymphocytes infiltrated into tumor tissues in the TG/GG genotype.
CONCLUSIONS: The IL-28B genotype is associated with HCC recurrence, gene expression, and histologic findings in patients with CHC. ©2013 AACR.
PURPOSE: Several single-nucleotide polymorphisms (SNP) in the interleukin-28B (IL-28B) locus have recently been shown to be associated with antiviral treatment efficacy for chronic hepatitis C (CHC). However, such an association with hepatocellular carcinoma (HCC) is unkno3 we investigated the association between the IL-28B genotype and the biology and clinical outcome of patients with HCC receiving curative treatment. EXPERIMENTAL
DESIGN: Genotyping of 183 patients with HCC with CHC who were treated with hepatic resection or radiofrequency ablation (RFA) was carried out, and the results were analyzed to determine the association between the IL-28B genotype (rs8099917) and clinical outcome. Gene expression profiles of 20 patients with HCC and another series of 91 patients with CHC were analyzed using microarray analysis and gene set enrichment analysis. Histologic and immunohistochemical analyses were also conducted.
RESULTS: The TT, TG, and GG proportions of the rs8099917 genotype were 67.8% (124 of 183), 30.6% (56 of 183), and 1.6% (3 of 183), respectively. Multivariate Cox proportional hazard analysis showed that the IL-28B TT genotype was significantly associated with HCC recurrence (P = 0.007; HR, 2.674; 95% confidence interval, 1.16-2.63). Microarray analysis showed high expression levels of IFN-stimulated genes in background liver samples and immune-related genes in tumor tissues of the IL-28B TG/GG genotype. Histologic findings showed that more lymphocytes infiltrated into tumor tissues in the TG/GG genotype.
CONCLUSIONS: The IL-28B genotype is associated with HCC recurrence, gene expression, and histologic findings in patients with CHC. ©2013 AACR.
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Year: 2013
PMID： 23426277 DOI： 10.1158/1078-0432.CCR-12-1641
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531