Wnt诱导分泌型蛋白1：研究乙型肝炎诱发肝癌的新途径  

WISP-1： a novel mediator of hepatitis B virus-related hepatocellular carcinoma

作　　者：蒋翔[1] 汪志军[2] 谢琼慧[2] 刘庆[2] 林菊生[2] 

机构地区：[1]武汉大学中南医院消化内科,430071 [2]华中科技大学附属同济医院肝病研究所

出　　处：《中华肝脏病杂志》2013年第4期285-289,共5页Chinese Journal of Hepatology

摘　　要：目的观察由乙型肝炎病毒x蛋白（HBX）引起的HepG2细胞内Wnt诱导分泌型蛋白1（WISP-1）的变化，探索HBV诱发肝癌的机制。方法收集肝癌、癌旁及正常肝组织标本，用免疫组织化学法检测标本中HBX和WISP-1的表达差异。设立2个实验组：稳定转染HBx基因的HepG2细胞（Gx）组和稳定转染空载体pc-DNA3．1（＋）HepG2细胞（G0）组。同时用PeR和Westemblot检测两组细胞中WISP-1的表达。计数资料样本率比较用x2检验；计量资料均数的比较用f检验和单因素方差分析；相关分析采用Spearman秩相关系数检验。结果肝癌组织中WISP-1的表达阳性率为76．6％，较癌旁组织的23．舭及正常肝组织的0明显增高，x2=35．967，P〈0．01，差异有统计学意义。Gx细胞中WISP-1mRNA和蛋白的相对表达水平分别为1170．33±41．26、240．33±11．37，与GO细胞中WISP-1的mRNA和蛋白相对表达水平265．34±27．47、40．33±7．09比较；t=31．625，F=600．565，P值均〈0．01，差异均有统计学意义。结论WISP-1基因在肝癌中呈高表达，HBV感染肝细胞后，其HBX可通过上调WISP-1的表达水平引起肝癌的发生。Objective To explore the effect of hepatitis B virus （HBV） X protein （HBX） on expression of the host gene Wnt induced secreted protein-1 （WISP-l） that is related to the pathogenic process of hepatocellular carcinoma （HCC）. Methods Tumor and paratumor tissues were collected from HCC patients, and normal liver tissues were collected from healthy controls. Immunohistochemistry was used to evaluate the in vivo presence and expression levels of HBX and WISP-1 in the three tissue types. HepG2 cells stably transfected with pc-DNA3.1 （＋）-HBX or with pc-DNA3.1 （＋） only （GO, control） were generated and used to examine in vitro the HBX-induced changes in WISP-1 expression at the mRNA and protein levels by reverse transcription polymerase chain reaction and western blotting, respectively. Results The HCC tissues showed significantly higher rates of positivity for WISP-1 expression than the non-tumor controls （76.6% vs. paratumor： 23.4% or normal tissues： 0%,2,2 = 35.967, P 〈 0.01）. HBX increased WISP-1 expression in HepG2 cells at both the mRNA （1170.33± 41.26 vs. G0： 265.34 ± 27.47, t = 31.63,P 〈 0.01） and protein （240.33 ± 11.37 vs. G0： 40.33 ± 7.09, F = 600.57, P 〈 0.01） levels. Conclusion HBV may up-regulate expression of the host gene WISP-1 through its X protein and thus promote the development of HCC.

关 键 词：肝炎 乙型 肝肿瘤 乙型肝炎病毒X蛋白 Wnt诱导分泌型蛋白1 

分 类 号：R735.7[医药卫生—肿瘤]