CEP 170在肝癌中的表达及对肝癌细胞增殖的影响  

Analysis of CEP 170 expression in liver cancer and its role in proliferation of liver cancer cells

作　　者：刘静 牛亚楠 孙力超 LIU Jing;NIU Yanan;SUN Lichao(National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100021,China)

机构地区：[1]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院,北京100021

出　　处：《转化医学杂志》2021年第5期275-280,286,共7页Translational Medicine Journal

基　　金：国家自然科学基金(81773170)。

摘　　要：目的研究中心体蛋白170(centrosomal protein 170,CEP 170)在肝癌组织中的表达及其对肝癌细胞增殖能力的影响。方法从临床蛋白质组学肿瘤分析联合会(clinical proteomic tumor analysis consortium,CPTAC)数据库下载肝癌蛋白质组学数据及临床信息,R包limma分析肿瘤组织与正常组织CEP 170蛋白表达差异,UALCAN及cBioPortal在线分析TCGA数据库中CEP 170转录水平及基因拷贝数变异。利用Kaplan-Meier法进行生存分析,ROC曲线分析检验预测效应。免疫组化(immunohistochemistry,IHC)验证肿瘤组织与正常组织表达差异。特异性siRNA敲降肝癌细胞株Huh-7 CEP 170表达,CCK-8法检测细胞增殖能力,平板克隆实验观察细胞克隆形成能力差异,流式细胞仪分析细胞周期变化。结果肝癌组织中CEP 170蛋白及转录水平显著高于正常组织(P<0.001),CEP 170高表达是患者预后不良的独立风险因素。基因组DNA拷贝数在6%的癌组织中存在扩增。IHC结果可见CEP 170在肿瘤组织中表达异常升高。敲降肝癌细胞Huh-7的CEP 170表达后,细胞增殖及克隆形成能力显著降低(P<0.001),细胞周期发生G 0/G 1期阻滞。结论CEP 170在肝癌组织中异常高表达,降低CEP 170表达能够显著抑制人肝癌细胞Huh-7增殖且细胞周期发生G 0/G 1期阻滞,CEP 170是肝癌治疗的潜在靶点。Objective To study the expression of Centrosomal Protein 170(CEP 170)in liver cancer tissues and its effect on the proliferation of liver cancer cells.Methods The liver cancer proteomics data and clinical information were downloaded from CPTAC(clinical proteomic tumor analysis consortium)database.The limma R package was used to analyze the differently expressed genes between cancer and adjacent tissues.The UALCAN and cBioPortal on‐line webserver were used to ayalyse the CEP 170 transcriptome and gene copy number in TCGA database.Kaplan-Meier method was used for survival analysis,and receiver operating characteristic(ROC)curve analysis was used to test the predictive power.Immunohistochemistry(immunohistochemistry,IHC)was used to verify the difference of CEP 170 ex‐pression level between the cancer and adjacent tissues.Specific siRNA was used to knocked down the expression level of CEP 170 in liver cancer cell line Huh-7.CCK-8 method was used to detect cell proliferation ability,and plate cloning experiment was used to test the cell clone formation ability.Cell cycle change was analyzed by flow cytometry.Results The protein and transcription levels of CEP 170 in the liver cancer tissues were significantly higher than that of in the ad‐jacent tissues(P<0.001).The high expression of CEP 170 was an independent risk factor for poor prognosis.Genomic DNA copy number was amplified in 6%of the cancer samples.IHC results showed that the expression of CEP 170 was abnormally increased in cancer tissues.After knocking down the expression of CEP 170 in hepatocarcinoma cell line Huh-7,the cell proliferation and clonal formation ability was significantly reduced(P<0.001),and the cell cycle was blocked in G 0/G 1 phase.Conclusion CEP 170 is abnormally expressed in liver cancer tissues.Down-regulation of CEP 170 inhibits the proliferation of Huh-7 human liver cancer cells and the G 0/G 1 phase block of the cell cycle.CEP 170 is a potential target for the treatment of liver cancer.

关 键 词：肝癌 临床蛋白质组学肿瘤分析联合会 中心体蛋白170 细胞增殖 靶向治疗 

分 类 号：R735.7[医药卫生—肿瘤]