CLEC4M在肝细胞癌中的表达及临床意义  

Expression of CLEC4M in hepatocellular carcinoma and its clinical significance

作　　者：余君铭 陈静[1] 葛超[1] 陈陶阳[2] 谢海洋[3] 李锦军[1] 李红[1] YU Junming;CHEN Jing;GE Chao;CHEN Taoyang;XIE Haiyang;LI Jinjun;LI Hong(State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200032,China;Department of Etiology,Qi Dong Liver Cancer Institute,Qidong 226200,Jiangsu Province,China;Department of Hepatobiliary and Pancreatic Surgery,First Affiliated Hospital of Zhejiang University Medical College,Hangzhou 310003,Zhejiang Province,China)

机构地区：[1]上海交通大学医学院附属仁济医院,上海市肿瘤研究所癌基因与相关基因国家重点实验室,上海200032 [2]启东肝癌防治研究所病因研究室,江苏启东226200 [3]浙江大学医学院第一附属医院肝胆胰外科,浙江杭州310003

出　　处：《肿瘤》2020年第7期470-478,共9页Tumor

基　　金：国家自然科学基金资助项目(编号:81672832);上海市卫生计生系统优秀学科带头人培养计划(编号:2018BR20)。

摘　　要：目的:探讨C型凝集素域家族4,成员M(C-type lectin domain family 4,member M,CLEC4M)在正常肝、肝硬化、肝细胞癌(hepatocellular carcinoma,HCC)组织及其配对癌旁肝组织中的表达及其临床意义。方法:利用肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达综合(Gene Expression Omnibus,GEO)等数据库,筛选各个肝癌数据库中在HCC组织中表达明显下调的基因。利用GEO数据库分析正常肝、肝硬化及HCC组织中CLEC4M mRNA的表达水平。采用实时定量PCR检测83对HCC组织及其配对癌旁肝组织中CLEC4M mRNA的表达水平。利用肝细胞癌癌基因图谱数据库(Integrative Molecular Analysis of Hepatocellular Carcinoma,HCCDB)分析CLEC4M mRNA在多种肿瘤中的表达情况。分别采用免疫组织化学法检测236对HCC及其配对癌旁肝组织、10例正常肝组织和12例肝硬化组织中CLEC4M蛋白的表达水平;蛋白质印迹法检测8对HCC及其配对癌旁肝组织中CLEC4M蛋白的表达水平;再用Kaplan-Meier法分析癌旁肝组织中CLEC4M表达与患者总生存期之间的关系。结果:对GEO和TCGA数据库的检索结果以及对83对临床样品的检测结果显示,HCC组织中CLEC4M mRNA的表达水平明显低于癌旁肝组织(P值均<0.0001)。对GEO数据库的检索结果显示,CLEC4M mRNA在正常肝、肝硬化及HCC组织中的表达呈逐渐下降的趋势(P<0.05)。免疫组织化学法检测结果显示,236例HCC组织中仅6例为CLEC4M蛋白高表达,而配对癌旁肝组织中有157例为CLEC4M高表达。Kaplan–Meier生存期分析显示,癌旁肝组织中CLEC4M高表达患者的总生存期较CLEC4M低表达者明显延长(P<0.0001)。结论:HCC组织中CLEC4M低表达,而癌旁肝组织中CLEC4M高表达提示患者预后较好。Objective:To investigate the expression and clinical significance of C-type lectin domain family 4,member M(CLEC4M)in hepatocellular carcinoma(HCC).Methods:The expression level of CLEC4M mRNA was analyzed in normal liver tissues,cirrhosis tissues,HCC tissues and matched non-cancerous liver tissues from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO).The expression level of CLEC4M mRNA in various tumors was analyzed using Integrative Molecular Analysis of Hepatocellular Carcinoma(HCCDB)website.CLEC4M mRNA expression level in 83 pairs of HCC tissues and matched non-cancerous liver tissues was analyzed by real-time fluorescent quantitative PCR.The protein expression level of CLEC4M in 236 pairs of HCC tissues and matched non-cancerous liver tissues,10 normal liver tissues and 12 cirrhosis tissues was detected by immunohistochemistry(IHC).The expression level of CLEC4M protein in 8 pairs of HCC tissues and matched non-cancerous liver tissues from our lab was analyzed using Western blotting.The relationship between CLEC4M expression level in non-cancerous liver tissues and overall survival of patients was analyzed by Kaplan-Meier method.Results:The mRNA level of CLEC4M was significantly lower in HCC tissues than matched non-cancerous liver tissues from TCGA,GEO and our lab(all P<0.0001).Further analysis showed that CLEC4M level was gradually decreased in normal liver tissues,cirrhosis tissues and HCC tissues.There were only 6 HCC tissues with CLEC4M high expression,while 157 non-cancerous liver tissues with CLEC4M high expression.Moreover,the Kaplan–Meier survival analysis revealed that high CLEC4M expression in non-cancerous liver tissues was accompanied with the long survival time(P<0.0001).Conclusion:CLEC4M expression is decreased in HCC tissues and high CLEC4M expression in non-cancerous liver tissues predicts a good prognosis in HCC.

关 键 词：肝肿瘤 外源凝集素类 C型 肝硬化 预后 

分 类 号：R737.7[医药卫生—肿瘤]