四种肿瘤干细胞标志物在肝细胞癌组织及外周血循环肿瘤细胞中的表达差异及其预后价值  

The expression differences and prognostic value of four cancer stem cell markers in hepatocellular carcinoma tissues and circulating tumor cells in peripheral blood

作　　者：吴蕙 沈敏娜 孙云帆 张春燕 杨欣荣 王蓓丽 郭玮 潘柏申 Wu Hui;Shen Minna;Sun Yunfan;Zhang Chunyan;Yang Xinrong;Wang Beili;Guo Wei;Pan Baishen(Department of Laboratory Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Liver Surgery,Liver Cancer Institute,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Laboratory Medicine,Xiamen Branch,Zhongshan Hospital,Fudan University,Xiamen 361015,China)

机构地区：[1]复旦大学附属中山医院检验科,上海200032 [2]复旦大学附属中山医院肝肿瘤外科,上海200032 [3]复旦大学附属中山医院厦门医院检验科,厦门361015

出　　处：《中华检验医学杂志》2021年第11期1043-1050,共8页Chinese Journal of Laboratory Medicine

基　　金：精准医疗全流程质量控制和管理体系建设(2017YFC0910003);国家自然基金面上项目(81772263,81972000);复旦大学附属中山医院临床研究专项基金(2018ZSLC05);国家自然基金青年项目(81902139);上海市临床重点专科项目(shslczdzk03302);上海市医学重点专科项目(ZK2019B28);厦门市医疗卫生重点项目(YDZX20193502000002)。

摘　　要：目的探讨4种肿瘤干细胞(CSC)标志物(EpCAM、CD133、CD90和CD24)在肝细胞癌(HCC)组织和外周血循环肿瘤细胞(CTC)中的表达及其在HCC患者预后判断中的价值。方法选取2013年10月至2014年9月共50例肝细胞癌患者的HCC组织和其中29例术前外周血样本,分别采用流式细胞术或qRT-PCR检测HCC组织或外周血CTC中EpCAM、CD133、CD90和CD24的表达,并对患者进行随访获取临床资料(包括肿瘤直径、肿瘤数量、卫星灶、血管浸润、肿瘤包膜完整性、Edmondson分期、BCLC分期和肝硬化等)以及生存时间,比较4种标志物在HCC组织和外周血CTC中的表达与患者生存时间的相关性。结果EpCAM、CD133、CD90和CD24在HCC组织中的表达阳性率分别为66%(33/50)、18%(9/50)、60%(30/50)和56%(28/50),在外周血CTC中的表达阳性率分别为55%(16/29)、38%(11/29)、31%(9/29)和59%(17/29)。HCC组织中CD90表达水平与肝硬化发生呈正相关(P<0.05),CD133表达与患者5年存活率呈负相关(P<0.05)。外周血CTC中EpCAM和CD24表达水平与患者Edmondson分期密切相关(P值均小于0.05)。HCC组织CD133阳性的患者生存时间低于CD133阴性的患者(P<0.05);HCC组织或者CTC中EpCAM任一阳性的患者生存时间低于双阴性表达的患者(P<0.05);而实验患者的外周血CTC中CD90单阳性的患者生存时间低于CD90双阴性/双阳性或HCC组织单阳性的患者(P<0.01)。结论根据4种CSC标志物在HCC组织和外周血CTC中的不同表达特征可组合判断患者的预后生存时间提供参考信息,其中HCC组织中CD133表达可作为患者预后判断的指标之一。组织样本和血液样本检测可提供多样化检测的需求。Objective To investigate the expression of four cancer stem cell(CSC)markers(EpCAM,CD133,CD90 and CD24)in hepatocellular carcinoma tissues and peripheral blood circulating tumor cells(CTC),their value in the prognosis of patients with hepatocellular carcinoma.Methods A total of 50 hepatocellular carcinoma tissues and 29 peripheral blood sample from 50 patients with hepatocellular cancer treated in Zhongshan Hospital Fudan University from October 2013 to September 2014 were collected and analyzed by flow cytometry or qRT-PCR to examine the expression of EpCAM,CD133,CD90 and CD24.The clinical data of patients were collected,including tumor size,tumor number,satellite lesions,vascular invasion,Edmondson stage,BCLC stage and liver cirrhosis,etc.The correlation between the expression of four markers in hepatocellular carcinoma tissues and CTC with the clinical data and survival time of patients were compared.Results The positive expression rates of EpCAM,CD133,CD90 and CD24 in hepatocellular carcinoma tissues were 66%(33/50),18%(9/50),60%(30/50)and 56%(28/50);the positive expression rates in CTC were 55%(16/29),38%(11/29),31%(9/29)and 59%(17/29).CD90 expression in hepatocellular carcinoma tissue was positively correlated with the occurrence HCC liver cirrhosis(P<0.05),while CD133 expression was negatively correlated with the 5-year survival rate of patients(P<0.05).The expression of EpCAM and CD24 in peripheral blood CTC were closely related to the patient′s Edmondson stage(P<0.05).The survival time of patients with CD133 positive expression in hepatocellular carcinoma tissue was lower than those without CD133 expression(P<0.05);the survival rate of patients with EpCAM expressed in either tissue or peripheral blood CTC was lower than that of patients with EpCAM double negative expression(P<0.05).The survival rate of patients with CD90 negative in HCC tissue and positive in peripheral blood was lower than that in patients with double negative/double positive in tissue and peripheral blood or patients positive in hepa

关 键 词：肝细胞癌 循环肿瘤细胞 EPCAM CD133 CD90 CD24 预后 

分 类 号：R735.7[医药卫生—肿瘤]