Association of Interleukin-28B Genotype and Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis C

被引：55

作者：

Hodo, Yuji ^{[1
]}

Honda, Masao ^{[1
,3
]}

Tanaka, Akihiro ^{[1
]}

Nomura, Yoshimoto ^{[1
]}

Arai, Kuniaki ^{[1
]}

Yamashita, Taro ^{[1
]}

Sakai, Yoshio ^{[1
]}

Yamashita, Tatsuya ^{[1
]}

Mizukoshi, Eishiro ^{[1
]}

Sakai, Akito ^{[1
]}

Sasaki, Motoko ^{[2
]}

Nakanuma, Yasuni ^{[2
]}

Moriyama, Mitsuhiko ^{[4
]}

Kaneko, Shuichi ^{[1
]}

机构：

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Gastroenterol, Kanazawa, Ishikawa 9208641, Japan

[2] Kanazawa Univ, Grad Sch Med Sci, Dept Human Pathol, Kanazawa, Ishikawa 9208641, Japan

[3] Kanazawa Univ, Dept Adv Med Technol, Grad Sch Hlth Med, Kanazawa, Ishikawa 9208641, Japan

[4] Nihon Univ, Sch Med, Dept Internal Med 3, Tokyo, Japan

来源：

CLINICAL CANCER RESEARCH | 2013年 / 19卷 / 07期

关键词：

GENOME-WIDE ASSOCIATION; GENE SET ENRICHMENT; RADIOFREQUENCY ABLATION; INTERFERON-ALPHA; RISK-FACTORS; IL28B; VIRUS; EXPRESSION; THERAPY; LIVER;

D O I：

10.1158/1078-0432.CCR-12-1641

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Clin Cancer Res; 19(7); 1827-37. (C)2013 AACR.

引用

页码：1827 / 1837

页数：11

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