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结肠和肝脏肿瘤过表达基因的上调与人类肝细胞癌的不良预后标志物显著相关。

Upregulation of colonic and hepatic tumor overexpressed gene is significantly associated with the unfavorable prognosis marker of human hepatocellular carcinoma.

作者信息

Yu Jun-Xiong, Chen Qian, Yu Ya-Qun, Li Shu-Qun, Song Jian-Fei

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of Guilin Medical University Guilin 541199, Guangxi, People's Republic of China.

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University Guilin, 541001, Guangxi, People's Republic of China.

出版信息

Am J Cancer Res. 2016 Feb 15;6(3):690-700. eCollection 2016.

Abstract

Colonic hepatic tumor overexpressed gene (ch-TOG), a member of the highly conserved XMAP215 family of microtubule-associated proteins (MAPs), plays a crucial role in bipolar mitotic spindle assembly. Here, we performed proof-of-principle studies targeting ch-TOG for the development of HCC and further compared its prognostic significance with the clinicopathologic features of HCC. Quantitative real-time PCR was used to measure the expression level of ch-TOG mRNA in 207 cases of paired HCC and adjacent noncancerous liver tissues (ANLT). Additionally, immunohistochemistry was employed to identify ch-TOG protein in 71 HCC tissues. All HCC patients were divided into two groups according to the expression level of ch-TOG. Cumulative progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method, and the prognostic value of ch-TOG was further evaluated using the Cox proportional hazards regression model. Our studies suggested that ch-TOG is overexpressed in HCC tissues compared with ANLT. The ch-TOG level was correlated with other prognostic factors, including the hepatitis B surface antigen (HBsAg) (p = 0.030), median size (p = 0.008), clinical tumor-node-metastasis (TNM) stage (p = 0.002), and alpha-fetoprotein (AFP) level (p = 0.030). Kaplan-Meier survival analysis showed that increased ch-TOG was associated with reduced PFS (p = 0.002) and OS (p = 0.004). Multivariate Cox proportional hazards analysis identified ch-TOG as an independent prognostic factor for the PFS (hazard ratio [HR] = 1.479, 95% confidence interval [CI] = 1.028-2.127, p = 0.035) and OS (HR = 1.609, 95% CI = 1.114-2.325, p = 0.011) of the HCC patients. Increased ch-TOG represents a powerful marker for predicting poorer prognosis in the clinical management of HCC, and may serve as a potential molecular target for HCC therapies in the future.

摘要

结肠肝肿瘤过表达基因(ch-TOG)是微管相关蛋白(MAP)的高度保守的XMAP215家族的成员,在双极有丝分裂纺锤体组装中起关键作用。在此,我们针对ch-TOG开展了原理验证研究,以用于肝癌的治疗,并进一步将其预后意义与肝癌的临床病理特征进行比较。采用定量实时PCR检测207例配对的肝癌组织和癌旁非癌肝组织(ANLT)中ch-TOG mRNA的表达水平。此外,采用免疫组织化学方法检测71例肝癌组织中的ch-TOG蛋白。根据ch-TOG的表达水平将所有肝癌患者分为两组。采用Kaplan-Meier法估计累积无进展生存期(PFS)和总生存期(OS)曲线,并使用Cox比例风险回归模型进一步评估ch-TOG的预后价值。我们的研究表明,与ANLT相比,ch-TOG在肝癌组织中过表达。ch-TOG水平与其他预后因素相关,包括乙型肝炎表面抗原(HBsAg)(p = 0.030)、中位大小(p = 0.008)、临床肿瘤-淋巴结-转移(TNM)分期(p = 0.002)和甲胎蛋白(AFP)水平(p = 0.030)。Kaplan-Meier生存分析表明,ch-TOG升高与PFS降低(p = 0.002)和OS降低(p = 0.004)相关。多变量Cox比例风险分析确定ch-TOG是肝癌患者PFS(风险比[HR] = 1.479,95%置信区间[CI] = 1.028 - 2.127,p = 0.035)和OS(HR = 1.609,95% CI = 1.114 - 2.325,p = 0.011)的独立预后因素。ch-TOG升高是预测肝癌临床管理中预后较差的有力标志物,未来可能作为肝癌治疗的潜在分子靶点。

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