染色体杂合性缺失在肝细胞癌根治术后预后预测中的价值  

The value of chromosomal loss of heterozygosity in prognosis prediction of hepatocellular carcinoma patients with curative resection

作　　者：逄锦忠 钦伦秀[2] 王强庆 李雯 任宁[2] 叶青海[2] 刘银坤[2] 汤钊猷[2] 

机构地区：[1]青岛经济技术开发区第一人民医院普外科,266555 [2]复旦大学肝癌研究所、中山医院肝外科

出　　处：《中华实验外科杂志》2008年第4期452-454,共3页Chinese Journal of Experimental Surgery

基　　金：国家杰出青年科学基金资助项目（30325041）;国家科技攻关计划资助项目（2002BA711A02-4）

摘　　要：目的通过生存分析探讨染色体杂合性缺失（LOH）在肝细胞癌（HCC）患者根治术后预后预测中的价值。方法选取1P、8p、17p、4q、13q及16q共6条染色体上24个具有高度多态性的微卫星标记，对1999年1月至2000年5月225例行根治术的HCC石蜡标本应用微切割技术，获取纯净肿瘤DNA进行LOH检测，并分析LOH与HCC患者根治术后5年总体生存（OS）、元瘤生存（DFS）的关系。结果LOH在检测的染色体位点上发生明显。在单因素分析中，D8S298位点LOH的患者根治术后5年OS、DFS率皆明显低于无LOH的患者[（39±6）比（54±5），P〈0．05；（36±7）比（60±6），P〈0．01]。同样，在D1S199基因位点，LOH患者术后5年OS、DFS率亦显著低于无LOH者[（28±7）比（55±5）。P〈0．01；（29±8）比（53±5），P〈0．05]。在其他22个检测位点，未发现LOH与HCC术后生存相关。在多因素分析中，Cox比例风险模型显示D8S298、DIS199位点LOH分别是HCC患者根治术后DFS、OS较差的独立因素（P均〈0．05）。结论D8S298、D1S199位点LOH有可能分别成为HCC患者根治术后预测转移复发及总体生存的分子标记。Objective To explore the value of chromosomal loss of heterozygosity （LOH） in prognosis prediction of hepatocellular carcinoma （ HCC） patients with curative resection by survival analyses. Methods A total of 225 patients who underwent curative resection for HCC from January 1999 to May 2000 were enrolled. Genomic DNA was extracted from microdissected HCC paraffin-embedded tissue samples for LOH detection using 24 high-polymorphic microsatellite markers located at chromosomes 1p, 8p, 17p,4q, 13q and 16q, and its assoeiation with 5-year overall survival （OS） and disease-free survival （DFS） of patients was analyzed. Results LOH was frequent at chromosomal loci analyzed. In univariate analyses,D8S298 LOH in the entire cohort was associated with a statistically significant worse 5-year OS [ （39 ± 6） vs （54 ± 5）, P 〈 0. 05 ] and DFS [ （ 36 ± 7 ） vs （ 60 ± 6）, P 〈 0.01 ]. Likewise, cases with D1S199 LOH had a statistically significant worse 5-year OS [ （28 ± 7） vs （55 ± 5）, P 〈 0.01 ] and DFS [ （29± 8） vs （53±5）,P 〈0.05 ] than cases without D1S199 LOH. No statistically significant associations with OS or DFS were observed for any other marker we analyzed in this study. In a multivariate modet,D8S298 LOH and D1S199 LOH were independendy associated with decreased DFS （P 〈 0.05） and decreased OS （P 〈 0.05 ） in the entire cohort, respectively. Conclusion D8S298 LOH and D1S199 LOH may serve as biomarkers of metastatic recurrence and OS prediction in HCC patients after curative resection, respectively.

关 键 词：癌 肝细胞 杂合性缺失 预后 

分 类 号：R735.7[医药卫生—肿瘤]