循环肿瘤细胞在原发性肝细胞肝癌患者中预后预测价值的meta分析

Circulating tumor cells for predicting the prognostic of patients with primary hepatocellular carcinoma:a Meta-analysis

目的分析外周血循环肿瘤细胞(CTCs)对原发性肝细胞肝癌患者预后预测的临床价值。方法检索Pub Med、EMBase、Web of Science、Cochrane Library和中国知网等数据库中2016年11月以前发表的相关文献,根据设定的纳入和排除标准进行文献的筛选,采用Revman5.0软件分析危险比(HR)及其95%可信区间(95%CI)用于评价CTCs预测原发性肝细胞癌患者临床预后的价值。结果共纳入14篇符合标准的文献,包括909例原发性肝癌患者,其中CTCs阳性患者445例,CTCs阴性患者464例。Meta分析结果显示,CTCs阳性患者的总生存期(OS)短于CTCs阴性患者[HR=2.31,95%CI(1.55,3.42),P=0.0001],其它生存时间包括(RFS,TPP,TTR)也短于CTCs阴性患者[HR=3.17,95%CI(1.66,6.05),P=0.0005]。针对不同的CTCs检测手段进行分析显示,使用RT-PCR和Cell search检测的患者中,CTCs阳性患者的预后更差[RT-PCR:HR=2.86,95%CI(1.09,7.49),P=0.03][Cell search:HR=2.55,95%CI(1.7,3.82),P<0.0001],而用Flow Cytometry检测的患者两者预后水平未有统计学差异[HR=2.59,95%CI(0.97,6.89),P=0.06]。结论 CTCs阳性的原发性肝癌患者预后明显差于CTCs阴性患者,对原发性肝细胞癌患者进行外周血CTCs检测具有重要临床意义。

Objective To explore the prognostic value of circulating tumor cells （CTCs） for the prognosis predicting of pa- tients with Primary hepatocellular carcinoma （HCC）. Methods Database including PubMed, EMBase, Web of Science, Cochrane Library, and CNKI were conducted to search associated studies which were published before November,2016. The studies were set up according to the inclusion/exclusion criteria, and Revman 5.0 software was used to analyze hazard ratio（HR） and 95% confidence in- terval （ 95 % CI） of including studies for assessing the prognostic value of circulating tumor cells （CTCs） for the prognosis predicting of patients with Primary hepatocellular carcinoma. Results 14 studies were selected according to the standard of literature with a total of 909 Primary HCC patients, including 445 patients with CTCs positive and 464 patients with CTCs negative. The results of Meta-analy- sis showthat the overall survival of CTCs-positive patients was shorten then the CTCs-negative patients [ HR = 2. 31, 95% CI（ 1.55, 3.42 ） ,P = 0. 0001 ], and other survival time including RFS, TPP and TrR also shorten then the CTCs-negative patients [ HR = 3.17, 95% CI（ 1.66,6. 05 ）,P = 0. 0005 ]. Analysis of different methods for CTCs detection shows that CTCs-positive patients lead to worse prognosis then CTCs-negative patients in RT-PCR or Cell searchgroup [ RT-PCR ： HR = 2. 86, 95% CI （ 1.09,7.49 ）, P = 0.03 ] [ Cellsearch ： HR = 2. 55, 95% CI （ 1.7,3.82 ）, P 〈 0. 0001 ], while no significant difference in Flow Cytometry group [ HR = 2. 59, 95% CI （0. 97,6. 89）, P = 0.06 ]. Conclusion Our analysis suggests that CTCs positivity indicates poor OS and detection of CTCs in peripheral blood may have important value for predicting prognosis of Primary HCC.