HBV相关肝癌组织中釉丛蛋白表达及其临床价值

Expression of tuftelin protein and its clinical value in HBV-related liver cancer tissues

目的分析肝细胞癌(HCC)组织中釉丛蛋白(TUFT1)表达及其临床意义。方法分析TCGA数据库和Oncomine数据库中,有关肝癌及非癌组织TUFT1 mRNA表达的生物信息资料。经伦理委员会批准以自身配对法收集2009年1月至2014年12月住院的132例HCC患者术后癌及癌旁组织,用组织芯片和免疫组织化学法(IHC)分析肝组织中TUFT1表达情况。按IHC染色强弱程度将肝癌分为高TUFT1表达组和低/不表达组,结合临床资料进行组内及组间统计学分析临床病理特征,以及对5年总体生存期(OS)和无病生存期(DFS)进行相关性分析。对数据进行U检验、单因素与多因素回归分析及Kaplan-Meier生存分析。结果IHC染色显示癌组织TUFT1定位于细胞质中和细胞膜上,其表达阳性率在肝癌组为87.1%,显著高于癌旁组的64.4%(χ^(2)=18.563,P<0.001)。肝癌患者TUFT1表达强度与HBeAg阳性(χ^(2)=4.080,P=0.043)、瘤体大小(χ^(2)=9.388,P=0.002)、伴有血管侵犯(χ^(2)=14.885,P<0.001)、TNM分期(χ^(2)=13.516,P<0.001)及患者伴腹水(χ^(2)=5.940,P=0.015)等显著相关;高TUFT1表达与患者的OS和DFS均呈负相关(P<0.001)关系。结论TUFT1过表达与HBV复制、血管侵犯及预后差密切相关,有望成为肝癌诊断与预后的有用标志物。

Objective To analyze the expression of tuftelin protein(TUFT1)and its clinical value in hepatocellular carcinoma(HCC)-related liver cancer tissues.Methods The biological information data of TUFT1 mRNA expression in liver cancer and non-cancer tissues were analyzed from the TCGA and Oncomine database.After the approval of the ethics committee,the self-pairing method was used to collect the postoperative cancer and para-carcinoma tissues of 132 HCC cases hospitalized between January 2009 and December 2014.Tissue microarray and immunohistochemistry(IHC)were used to analyze the expression of TUFT1 in liver tissues.According to IHC staining,liver cancer was divided into high TUFT1 and low/no expression group.Combined with clinical data,the clinicopathological characteristics were statistically analyzed between and within the groups.The 5-year overall survival(OS)and disease-free survival(DFS)was analyzed by correlation analysis.Results IHC staining showed that TUFT1 in cancer tissue was localized in the cytoplasm and cell membrane,and its positive expression rate was significantly higher in the liver cancer group(87.1%)than the para-carcinoma group(64.4%)(χ^(2)=18.563,P<0.001).TUFT1 expression intensity in patients with liver cancer was significantly correlated with HBeAg positive(χ^(2)=4.080,P=0.043),tumor size(χ^(2)=9.388,P=0.002),vascular invasion(χ^(2)=14.885,P<0.001),TNM stage(χ^(2)=13.516,P<0.001)and ascites(χ^(2)=5.940,P=0.015).TUFT1 high expression was negatively correlated with OS and DFS(P<0.001).Conclusion The overexpression of TUFT1 is closely related to HBV replication,vascular invasion and poor prognosis,and it is expected to become a useful marker for liver cancer diagnosis and prognosis.