Gain of GRHL2 is associated with early recurrence of hepatocellular carcinoma

被引：69

作者：

Tanaka, Yasuo ^{[1
,2
]}

Kanai, Fumihiko ^{[1
,2
]}

Tada, Motohisa ^{[1
,3
]}

Tateishi, Ryosuke ^{[1
]}

Sanada, Masashi ^{[4
]}

Nannya, Yasuhito ^{[4
]}

Ohta, Miki ^{[1
]}

Asaoka, Yoshinari ^{[1
]}

Seto, Motoko ^{[1
]}

Shiina, Shuichiro ^{[1
]}

Yoshida, Haruhiko ^{[1
]}

Kawabe, Takao ^{[1
]}

Yokosuka, Osamu ^{[3
]}

Ogawa, Seishi ^{[5
]}

Omata, Masao ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, Tokyo 1138655, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Clin Drug Evaluat, Bunkyo Ku, Tokyo 1138655, Japan

[3] Chiba Univ, Grad Sch Med, Dept Med & Clin Oncol, Chiba 2608670, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan

[5] Univ Tokyo, Grad Sch Med, 21st Century COE Program, Bunkyo Ku, Tokyo 1138655, Japan

来源：

JOURNAL OF HEPATOLOGY | 2008年 / 49卷 / 05期

关键词：

Copy number alteration; Loss of heterozygosity; High-density single nucleotide polymorphism array; Genetic marker; Recurrence;

D O I：

10.1016/j.jhep.2008.06.019

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background/Aims: The aim of this study is to identify genomic changes that might be implicated in hepatocellular carcinoma (HCC) progression, and evaluate the associations with clinico-pathological features. Methods: The genomic DNA of 17 hepatoma cell lines was analyzed using Affymetrix GeneChip Human Mapping 50 K high-density oligonucleotide arrays. We selected representative genes from recurrent amplified regions and measured the copy number of these genes in 70 HCC clinical samples. Results: We found 10 recurrent high-grade gain regions spanning less than 3 Mb in at least two hepatoma cell lines, and selected 10 representative genes. The copy number was almost normal in non-cancerous tissue and frequently amplified in Edmondson grade II or III HCC compared to Edmondson grade I HCC. Gain of TAX1BP1 in 7p15.2-1 was associated with larger tumor size and positivity of HCV antibody, and gain of CCND1 in 11q13.2-3 was associated with larger tumor size by multivariate analysis. Furthermore, a gain of GRHL2 in 8q22.3 was associated with early recurrence of HCC, controlling for clinical parameters. Decreased GRHL2 expression by RNA interference inhibits the growth of hepatoma cells, suggesting its association with cell proliferation. Conclusions: A gain of GRHL2 might be a predictive marker for HCC recurrence. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：746 / 757

页数：12

共 56 条

[1] Simple and complex ABCR:: Genetic predisposition to retinal disease [J].