Clp蛋白酶复合体亚基ClpX在肝细胞癌中的表达及意义

目的探讨Clp蛋白酶复合体的ATP依赖性亚基(ATP-dependent Clp protease ATP-binding subunit,ClpX)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及临床意义.方法收集2013年1月至2014年12月于空军军医大学西京医院肝胆外科行根治性肝切除术的166例HCC患者癌组织及癌旁正常组织.采用免疫组化法检测HCC癌组织及相应癌旁正常组织中ClpX的表达,并分析ClpX蛋白表达与HCC患者临床病理特征及预后关系.在HCC癌细胞株SNU739中分别干涉或过表达ClpX后,采用MTS法检测细胞增殖能力.结果ClpX在HCC癌组织中的表达水平低于癌旁正常组织(P<0.001),ClpX高表达的HCC患者总生存期优于低表达患者(P=0.009).ClpX表达水平与TNM分期相关(P=0.008),ClpX低表达是影响HCC患者总生存期的独立危险因素(P=0.046).干涉ClpX表达后,SNU739细胞增殖能力较对照组增强(P<0.001);而过表达ClpX后,细胞增殖能力降低(P<0.001).结论ClpX在HCC癌组织中呈低表达,且低表达患者预后更差;下调ClpX可促进细胞增殖,ClpX可作为HCC患者潜在的预后标志物.

Expression and significance of Clp protease complex subunit ClpX in hepatocellular carcinoma

Objective To investigate the expression of ATP-dependent Clp protease ATP-binding subunit（ClpX） in hepatocellular carcinoma（HCC）and its clinical significance. Methods The HCC tissues and corresponding adjacent normal tissues of 166 patients with HCC who underwent radical hepatectomy at the Department of Hepatobiliary Surgery，Xijing Hospital of Air Force Military Medical University from January 2013 to December 2014 were collected. The expression of ClpX in HCC tissues and corresponding adjacent normal tissues was detected by Immunohistochemical staining，and the relationship between the expression of ClpX protein and the clinicopathological characteristics and prognosis of HCC patients was analyzed. After interfered and overexpressed with ClpX，respectively，in HCC cell line SNU739，the cell proliferation was detected by MTS assay. Results The expression of ClpX in HCC tissues was significantly lower than that in adjacent normal tissues（P<0.001），and the overall survival of HCC patients with high ClpX expression was significantly better than that of patients with low ClpX expression （P=0.009）. The expression of ClpX was negatively related to TNM stage （P=0.008），and low ClpX expression was an independent risk factor affecting the overall survival of HCC patients （P=0.046）. After interfered with the ClpX expression，the proliferation ability of SNU739 cells was significantly higher than that of the control group （P<0.001），while the proliferation ability of SNU739 cells decreased significantly after overexpression of ClpX（P<0.001）. Conclusions ClpX is lowly expressed in HCC tissues，the patient with low expression of ClpX has a poorer prognosis，and down-regulation of ClpX can promote cell proliferation. ClpX may serve as a potential prognostic marker for patients with HCC.