循环肿瘤细胞检测对非小细胞肺癌的诊断价值

Diagnostic value of human circulating tumor cell detection for non-small cell lung cancer

目的评估循环肿瘤细胞检测对非小细胞肺癌（NSCLC）的诊断价值。方法采用非干预型临床研究，选择2014年10月至2015年4月就诊于上海市胸科医院胸外科的162例NSCLC患者（其中I期83例、Ⅱ期16例、Ⅲ期27例、Ⅳ期36例），119例肺部良性疾病患者，以及同期接受体检的52名健康人。采用基于叶酸受体的PCR方法检测外周血循环肿瘤细胞（CTC）水平，流式荧光发光法检测CEA、CYFRA21—1，化学发光微粒子免疫法检测SCC，多组比较采用Kruskal—Wallis检验，两组比较采用Mann—WhitneyU检验，阳性率比较采用卡方检验，并绘制ROC曲线分析。结果NSCLC患者的CTC中位数为11．90CTCUnits／3ml，显著高于肺部良性疾病患者（6．72CTCUnits／3m1）和健康人（5．82CTCUnits／3m1），差异有统计学意义（x2=125．990，P〈0．01）；ROC曲线下面积为0．8532（95％CI：0．8095～0．8969），临界值（cut—off值）为8．74CTCUnits／3ml，对应的灵敏度为77．16％，特异度为90．06％。临床I期NSCLC患者的CTC阳性率为68．7％，明显高于多联肿瘤标志物（CEA＋CYFRA21—1＋SCC）的阳性率（19．4％），差异有统计学意义（0=32．98，P〈0．01）。结论CTC检测对NSCLC诊断具有较好的灵敏度和特异度，可能有一定的临床应用价值。

Objective To estimate the diagnostic value of circulating tumor cell detection for non- small cell lung cancer. Methods A Non-intervention clinical study was conducted in this research. From October 2014 to April 2015, totally 162 NSCLC who presented at Thoracic Surgery Department, 119 benign pulmonary disease and 52 healthy individuals were collected from Shanghai Chest Hospital. Folate receptor （FR） based polymerase chain reaction （PCR） method was used to detect the circulating tumor cell （CTC） level, CEA and CYFRA21-1 was detected by the flowcytometry fluorescence luminance method, SCC was detected with Chemiluminescent microparticle immunoassay. The differences among groups were analyzed by the Kmskal-Wallis test（ multi group comparison） and the Mann-Whitney U test（ two group comparison）, and the chi-square test was used in the positive rate comparison; the Receiver Operating Characteristics （ROC） curve was established. Results The median level of CTC in NSCLC patients was 11.90 Units/3 ml, which was significantly higher than those of benign pulmonary disease （6. 72 CTC Units/3 ml ） and healthy individuals （5.82 CTC Units/3 ml, X2 = 125. 990, P 〈 0. 01 ）. Areas Under Curve （AUCs） of ROC curve for NSCLC was 0. 853 2 （ 95% CI： O. 809 5,0. 896 9 ）. The cut-off value for discriminating NSCLC with benign pulmonary disease/healthy people was 8.74 CTC Units/3 ml with sensitivity being 77.16% and specificity being 90. 06%. The positive rate of CTC in Stage I NSCLC patients was 68.7%, which was much higher than that of the combination of tumor markers （ X2 = 32. 98, P 〈 0. 01 ）. Conclusion With relatively high sensitivity and specificity, the detection of cireulating tumor cell may has a clinical value of application and extension.