Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular carcinoma.
Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular carcinoma.
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DOI：
10.1186/1476-4598-9-74
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发表时间：
2010-04-09
期刊：
影响因子：
37.3
通讯作者：
Rusyn I
中科院分区：
文献类型：
--
作者：
Tsuchiya M;Parker JS;Kono H;Matsuda M;Fujii H;Rusyn I
本研究的目的是了解丙型肝炎病毒（HCV）感染患者肝细胞癌（HCC）复发的基因表达特征。HCV感染者肝癌根治性切除术后的无复发生存期（RFS）是高度可变的。传统的临床病理学终点被认为是RFS的弱预测因子。已经表明，HCC和非肿瘤肝组织的基因表达谱可以改善RFS的预测，有助于了解潜在的肝脏疾病，并指导个体化的患者管理。肿瘤和非肿瘤肝脏的冷冻样本来自47名HCV相关HCC患者。从患有转移性肝肿瘤的无HCV受试者获得额外的非肿瘤肝样品。基因表达谱数据用于确定HCV相关HCC的分子特征，并开发RFS的预测因子。HCV相关HCC的分子特征证实了MYC和TGFβ1在肝肿瘤发展中的中心作用。肿瘤中的基因表达对RFS的预测能力较差，但对晚期复发（>1年）受试者的非肿瘤组织分析产生了RFS的强预测因子。重要的是，RFS的非肿瘤组织来源的基因表达预测因子在单变量和多变量考克斯比例风险模型分析中均高度显著。HCV相关HCC患者的非肿瘤组织的微阵列分析提供了RFS的新分子特征，特别是在晚期复发患者中。基因表达预测因子可能对肝癌复发和肝癌患者肿瘤形成的病理生物学有重要意义。
The goal of this study was to understand gene expression signatures of hepatocellular carcinoma (HCC) recurrence in subjects with hepatitis C virus (HCV) infection. Recurrence-free survival (RFS) following curative resection of HCC in subjects with HCV is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized patient management. Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGFβ1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression predictor may hold important insights into the pathobiology of HCC recurrence and de novo tumor formation in cirrhotic patients.
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影响因子：
11.2
作者：
Hoshida Y;Nijman SM;Kobayashi M;Chan JA;Brunet JP;Chiang DY;Villanueva A;Newell P;Ikeda K;Hashimoto M;Watanabe G;Gabriel S;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
5.8
作者：
Benito, M;Parker, J;Marron, JS
通讯作者：
Marron, JS
影响因子：
13.5
作者：
Matsuzaki, Koichi;Murata, Miki;Seki, Toshihito
通讯作者：
Seki, Toshihito
DOI：
10.1152/ajprenal.00142.2007
发表时间：
2008-05-01
影响因子：
4.2
作者：
Elberg, Gerard;Chen, Lijuan;Turman, Martin A.
通讯作者：
Turman, Martin A.