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

doi:10.3760/cma.j.cn371439-20200116-00002

Abstract

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

Tian Linghan, Zhu Ling, Liu Xin, Ye Jingwen, He Jiahui, Wang Xicai. Level of peripheral blood circulating tumor cells in lung cancer patients detected by CI-101 and its clinical significance[J]. Journal of International Oncology, 2020, 47(4): 199-204.

Figures/Tables 6

掺入细胞数(个)	回收细胞数(个, $x ˉ$ ±s)	回收率(%)
50	36±6	72.0
100	85±12	85.0
200	178±15	89.0
500	420±30	84.0
1 000	782±45	78.0

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组别	CTC检出数	H值	P值
肺癌患者组(n=100)	58(42)^ab
肺部良性肿瘤患者组(n=40)	26(8)	51.874	<0.001
健康志愿者组(n=30)	26(23)

临床病理特征	CTC阳性 (n=85)	CTC阴性 (n=15)	阳性率 (%)	χ²值	P值
年龄(岁)
<50	17	1	94.4	0.765	0.382
≥50	68	14	82.9
性别
男性	59	11	84.2	0.093	0.760
女性	26	4	86.7
TNM分期
Ⅰ~Ⅱ期	14	11	50.0	19.059	<0.001
Ⅲ~Ⅳ期	71	4	94.4
肿瘤大小(cm)
<3	15	10	57.7	13.830	<0.001
≥3	70	5	86.5
病理类型
鳞状细胞癌	14	3	82.3	2.152	0.348
腺癌	44	10	81.5
其他	27	2	93.1
远处转移
有	72	8	77.5	6.005	0.014
无	13	7	45.0