伴门静脉癌栓的肝癌手术预后相关基因的筛选  

Identification and Validation of a Novel Gene Signature Associated with Surgical Outcome of Human Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

作　　者：邹如海[1] 韩峰[1] 李安华[1] 洪健[2] 石明[2] Kam M. Hui 元云飞[2] 

机构地区：[1]华南肿瘤学国家重点实验室／／中山大学肿瘤防治中心超声科,广东广州510060 [2]华南肿瘤学国家重点实验室／／中山大学肿瘤防治中心肝胆科,广东广州510060 [3]新加坡国立癌症中心Humphrey Oei肿瘤研究所,169610

出　　处：《中山大学学报（医学科学版）》2011年第3期342-347,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(30872489)

摘　　要：【目的】全基因芯片技术筛选伴肉眼门静脉癌栓(PVTT)肝细胞癌患者的基因谱,并进一步分析筛选出的基因的临床预测价值。【方法】40例伴有PVTT的肝癌根据术后中位生存期分为2组:长生存期组与短生存期组,采用全基因芯片技术和交叉检验重复抽样方法筛选出具有表达差异的基因谱,并进一步采用免疫组织化学方法验证筛选出的基因的临床意义。【结果】本研究共筛选出的10个表达差异显著的基因,包括AKR1C1、TARDBP、EIF4E、MFN1、SNRNP25、LOC55908、ARPP19、RORC、PEX11B和EGFR2,对伴有PVTT的肝癌术后长生存期患者的预测准确性达95%,特异性100%,假阳性率0。其中肝癌相关基因TD26(Hepatocellular carcinoma associated-gene TD26)在长生存期组中表达明显上调(P<0.001),免疫组化染色验证TD26蛋白在长生存期组病例中表达显著高于短生存期组(P=0.016)。【结论】本研究筛选出的10个基因有可能作为伴有PVTT的肝细胞癌患者手术预后的预测指标;TD26在伴PVTT的肝癌术后长期生存患者中表达增高。[Objective]To identify and validate a gene signature to predict prognosis and select suitable surgical candidate for HCC with PVTT（portal vein tumor thrombus） by microarray gene profiling.[Methods] Forty HCC with PVTT cases were divided into two groups：long-term survival and short-term survival,according to their median survival.Gene profiling study and a 3-fold cross-validation and resampling method were performed to pick up candidate genes,and then immunohistochemistry（IHC） study was used to validate the microarray results.[Results] Ten candidate genes including AKR1C1,TARDBP,EIF4E,MFN1,SNRNP25,LOC55908,ARPP19,RORC,PEX11B,and EGFR2 were selected by microarray.The sensitivity,specificity,and false positive rates for selecting postoperative longer survivor in HCC patients with PVTT were 95%,100%,and 0%,respectively.Hepatocellular carcinoma associated gene TD26（LOC55908） was the most significant up-regulated gene in longer survivors（fold-change=9.51,P 〈0.001）.The expression of TD26 in longer survivors was validated by IHC study（P = 0.016）.[Conclusion]Our data demonstrate that these 10 genes expression signature could be a novel biomarker to predict prognosis for HCC patients with PVTT.

关 键 词：肝肿瘤 肝切除术 基因表达谱 肝癌相关基因TD26 预后 

分 类 号：R735.9[医药卫生—肿瘤]