CellSearch技术检测非小细胞肺癌患者外周血中循环肿瘤细胞数并分析其与预后的相关性

Number of circulating tumor cells in peripheral blood of patients with non-small cell lung cancer detected by CellSearch and its correlation with prognosis

目的:通过CellSearch技术检测非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血中循环肿瘤细胞(circulating tumor cells,CTCs)的数目,并探讨其与NSCLC患者预后的相关性。方法:回顾分析2013年6月—2017年6月在吉林省肿瘤医院接受治疗的68例NSCLC患者的资料。所有患者采集外周静脉血10 mL,经CellTracks Autoprep System进行磁珠法富集CTCs,采用CellTracks AnalyzerⅡ系统扫描分析CTCs的个数,将EpCAM+CK+DAPI+CD45-且细胞膜及细胞核染色完整的细胞定义为CTCs,CTCs数目≥1定义为CTCs阳性。采用χ^2检验分析CTC数目与NSCLC患者病理参数的相关性;采用Kaplan-Meier法进行生存分析,COX风险回归模型计算危险比(hazard ratio,HR)和95%可信区间(con dence interval,CI)分析CTCs对NSCLC患者总生存期的影响。结果:68例NSCLC患者中18例有CTCs,CTCs阳性率为26.5%(18/68)。Ⅰ+Ⅱ期、Ⅲ期及Ⅳ期患者的CTCs阳性率分别为23.1%(3/13)、25.0%(4/16)和28.2%(11/39);肺腺癌与肺鳞癌患者CTCs阳性率分别为30.4%(14/46)和18.2%(4/22)。多因素回归分析结果显示,病理类型、病理分期和治疗方式均不是CTCs影响预后生存的因素(P值均>0.05)。CTCs数目≥1患者总生存时间明显短于CTCs数目<1患者(HR=0.381,95%CI:0.151~0.963,P=0.041),但CTCs的存在与病理类型、年龄及吸烟无关(P=0.383,P=1.000和P=1.000)。结论:在Ⅰ~Ⅳ期NSCLC患者外周血中均可检测到CTCs,以Ⅳ期患者中检出率最高;CTCs数目≥1患者的生存时间明显短于CTCs数目<1者。CTCs可能是一种有一定临床应用价值的检测指标。

Objective:To detect the number of circulating tumor cells(CTCs)in peripheral blood of the patients with non-small cell lung cancer(NSCLC)by CellSearch technique,and to explore the correlation between the number of CTCs and the prognosis of NSCLC patients.Methods:The data of 68 patients with NSCLC treated in Jilin Cancer Hospital from June 2013 to June 2017 were retrospectively analyzed.The peripheral venous blood was collected for 10 mL per patient,and the CTCs were enriched by magnetic beads using CellTracks Autoprep System.The number of CTCs was analyzed by CellTracks AnalyzerⅡsystem,and the EpCAM+CK+DAPI+CD45-cells which complete stained in membrane and nucleus were defined as CTCs.The number of CTCs≥1 was defined as the positive.The correlation between the number of CTCs and the pathological parameters was analyzed by chi-square test,and COX risk regression model was used to analyze the impact of CTCs on overall survival of patients with NSCLC by hazard ratio(HR)and 95%confidence interval(CI).Results:The positive rate of CTCs was 26.5%(18/68)in the patients with NSCLC.The positive rates of CTCs in the patients with stageⅠ+Ⅱ,Ⅲ,andⅣwere 23.1%(3/13),25.0%(4/16),and 28.2%(11/39),respectively.Moreover,the positive rates of CTCs in the patients with lung adenocarcinoma and lung squamous cell carcinoma were 30.4%(14/46)and 18.2%(4/22),respectively.COX multivariate regression analysis showed that pathological type,pathological stage and treatment method were not CTCs-influencing factors on prognosis(all P>0.05).The survival time of patients with CTC number≥1 was significantly shorter than that of patients with CTC number<1(P=0.041,HR=0.381,95%CI:0.151-0.963).However,the persence of CTCs was not associated with pathological type,age and smoking status(P=0.383,P=1.000,and P=1.000).Conclusion:CTCs can be detected in peripheral blood of the patients with stageⅠ-Ⅳof NSCLC,and the rate of detection was highest in the patients with stageⅣof NSCLC.The survival time of patients with CTC number≥1 is significantly shorter than that of the patients with CTC number<1,suggesting that CTC number is a valuable indicator for clinical application.