国际肿瘤学杂志

国际肿瘤学杂志 ›› 2020, Vol. 47 ›› Issue (4): 199-204.doi: 10.3760/cma.j.cn371439-20200116-00002

• 论著 • 上一篇    下一篇

CI-101检测肺癌患者外周血循环肿瘤细胞水平及其临床意义

田翎含1, 朱玲2, 刘馨1, 叶静雯1, 何嘉慧1, 王熙才1()   

  1. 1 昆明医科大学第三附属医院 云南省肿瘤医院肿瘤研究所 650118
    2 昆明市第一人民医院肿瘤科 650034
  • 收稿日期:2020-01-16 修回日期:2020-03-11 出版日期:2020-04-08 发布日期:2020-05-26
  • 通讯作者: 王熙才 E-mail:wangxc2005323@126.com
  • 基金资助:
    国家自然科学基金(81460358);云南省卫生科技计划(2017NS201);云南省卫生科技计划(2018NS0078);云南省科技计划(2017FE467(-189));云南省科技计划(2014FB066)

Level of peripheral blood circulating tumor cells in lung cancer patients detected by CI-101 and its clinical significance

Tian Linghan1, Zhu Ling2, Liu Xin1, Ye Jingwen1, He Jiahui1, Wang Xicai1()   

  1. 1 Cancer Research Institute, Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming 650118, China
    2 Department of Oncology, First People's Hospital of Kunming, Kunming 650034, China
  • Received:2020-01-16 Revised:2020-03-11 Online:2020-04-08 Published:2020-05-26
  • Contact: Wang Xicai E-mail:wangxc2005323@126.com
  • Supported by:
    National Natural Science Foundation of China(81460358);Yunnan Provincial Health Technology Plan(2017NS201);Yunnan Provincial Health Technology Plan(2018NS0078);Yunnan Provincial Science and Technology Plan(2017FE467(-189));Yunnan Provincial Science and Technology Plan(2014FB066)

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摘要：

目的 应用CI-101细胞搜寻免疫磁珠富集技术结合荧光细胞化学染色方法,探讨肺癌患者外周静脉血中循环肿瘤细胞(CTC)水平与肺癌患者临床病理特征及生物标志物之间的相关性。方法 采集2014年3月至2014年9月云南省肿瘤医院胸外科和胸心外科收治的100例首诊肺癌患者、40例肺部良性肿瘤患者(均经过病理活检确诊)及体检中心30例健康志愿者的血样。应用CI-101细胞搜寻免疫磁珠富集外周血中的CTC,应用免疫细胞荧光技术对CTC行形态学分析,并用HE细胞染色方法鉴定肿瘤细胞。检测CI-101细胞搜寻仪对CTC的回收率、灵敏度、特异度;比较肺癌患者、肺部良性肿瘤患者及健康志愿者外周血CTC阳性率的区别;分析肺癌患者CTC阳性率与患者临床病理特征之间的关系;采用列联系数分析肺癌患者及肺部良性肿瘤患者CTC与血清肿瘤标志物之间的相关性。结果 用CI-101细胞搜寻仪检测CTC回收率为72.0%~89.0%,且回收的细胞数与掺入细胞数有显著线性相关性,相关系数r=0.998(P<0.001),线性回归方程为:y=0.781x+11.307,灵敏度为85.0%,特异度为71.4%。肺癌患者组CTC阳性率(85.0%,85/100)高于肺部良性肿瘤患者组(15.0%,6/40)及健康志愿者组(46.7%,14/30)(χ 2=62.798,P<0.001);CTC阳性率与肺癌患者TNM分期(χ 2=19.059,P<0.001)、肿瘤大小(χ 2=13.830,P<0.001)、有无远处转移(χ 2=6.005,P=0.014)均相关。肺癌患者及肺部良性肿瘤患者CTC阳性与血清肿瘤标志物CEA(φ=0.217,P=0.011)、CA125(φ=0.198,P=0.020)、CA199(φ=0.169,P=0.049)、CA742(φ=0.186,P=0.037)、细胞角蛋白19片段(φ=0.461,P<0.001)呈正相关。结论 应用CI-101细胞搜寻仪联合免疫磁珠法可成功富集肺癌患者外周静脉血中的CTC,肺癌患者的CTC阳性率与患者的肿瘤大小、TNM分期、有无远处转移、血清肿瘤标志物有明显相关性,可作为肺癌患者病情监测的辅助指标。

关键词: 肿瘤细胞,循环, 肺肿瘤, 液态活检

Abstract:

Objective To explore the correlations between circulating tumor cells (CTCs) level in peripheral venous blood and clinicopathological characteristics and biomarkers of lung cancer patients using CI-101 cell search immunomagnetic bead enrichment technology combined with fluorescent cytochemical staining. Methods Blood samples were collected from 100 patients with first-diagnosed lung cancer treated in Department of Thoracic Surgery and Department of Cardiothoracic Surgery of Yunnan Cancer Hospital from March 2014 to September 2014, 40 patients with lung benign tumor (all confirmed by pathological biopsy) and 30 healthy volunteers from the physical examination center. CTCs in peripheral blood were enriched by CI-101 cell search immunomagnetic bead, the morphology of CTCs was analyzed by immunocytofluorescence technique, and tumor cells were identified using HE cell staining method. The recovery rate, sensitivity and specificity of CI-101 cell search instrument for CTCs were detected. The difference of positive rate of CTCs in peripheral blood among lung cancer patients, lung benign tumor patients and healthy volunteers was compared. The relationship between the positive rate of CTCs and the clinicopathological characteristics of patients with lung cancer was analyzed. The correlations between CTCs and serum tumor markers were analyzed by coefficient of contingency in patients with lung cancer and lung benign tumor. Results The recovery rate of CTCs by CI-101 cell search instrument was 72.0%-89.0%, and there was a significant linear correlation between the number of recovered cells and the number of incorporated cells. The correlation coefficient r=0.998 (P<0.001), the linear regression equation was y=0.781x+11.307, the sensitivity was 85.0%, and the specificity was 71.4%. The positive rate of CTCs in lung cancer patients (85.0%, 85/100) was higher than that in lung benign tumor patients (15.0%, 6/40) and healthy volunteers (46.7%, 14/30) (χ 2=62.798, P<0.001). The positive rate of CTCs in lung cancer patients was correlated with TNM stage (χ 2=19.059, P<0.001), tumor size (χ 2=13.830, P<0.001) and distant metastasis (χ 2=6.005, P=0.014). Coefficient of contingency analysis showed that the positive of CTCs was positively correlated with serum tumor markers CEA (φ=0.217, P=0.011), CA125 (φ=0.198, P=0.020), CA199 (φ=0.169, P=0.049), CA742 (φ=0.186, P=0.037) and cytokeratin 19 fragment (φ=0.461, P<0.001) in patients with lung cancer and lung benign tumor. Conclusion The application of CI-101 cell search instrument combined with immunomagnetic bead method can successfully enrich CTCs in peripheral venous blood of lung cancer patients. The positive rate of CTCs in patients with lung cancer has obvious correlation with tumor size, TNM stage, distant metastasis, serum tumor markers. It can be used as an auxiliary indicator for monitoring the condition of lung cancer patients.

Key words: Neoplastic cells,circulating, Lung neoplasms, Liquid biopsy