Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2020

Open Access 01-12-2020 | NSCLC | Research article

Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer

Authors: Jingyao Li, Yi Liao, Yaling Ran, Guiyu Wang, Wei Wu, Yang Qiu, Jie Liu, Ningyu Wen, Tao Jing, Haidong Wang, Shixin Zhang

Published in: BMC Pulmonary Medicine | Issue 1/2020

Login to get access

Abstract

Background

The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC).

Methods

CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up.

Results

The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P <  0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022).

Conclusions

CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed
3.
go back to reference Gridelli C, Rossi A, Carbone DP, Guarize J, Karachaliou N, Mok T, Petrella F, Spaggiari L, Rosell R. Non-small-cell lung cancer. Nat Rev Dis Primers. 2015;1:15009.PubMedCrossRef Gridelli C, Rossi A, Carbone DP, Guarize J, Karachaliou N, Mok T, Petrella F, Spaggiari L, Rosell R. Non-small-cell lung cancer. Nat Rev Dis Primers. 2015;1:15009.PubMedCrossRef
4.
go back to reference Aberle DR, Adams A, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. Reduced lung-cancer mortality with low-dose com-puted tomographic screening. N Engl J Med. 2011;365:395–409.PubMedCrossRef Aberle DR, Adams A, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. Reduced lung-cancer mortality with low-dose com-puted tomographic screening. N Engl J Med. 2011;365:395–409.PubMedCrossRef
5.
go back to reference Esposito A, Criscitiello C, Locatelli M, Milano M, Curigliano G. Liquid biopsies for solid tumors: understanding tumor heterogeneity and real time monitoring of early resistance to targeted therapies. Pharmacol Ther. 2016;157:120–4.PubMedCrossRef Esposito A, Criscitiello C, Locatelli M, Milano M, Curigliano G. Liquid biopsies for solid tumors: understanding tumor heterogeneity and real time monitoring of early resistance to targeted therapies. Pharmacol Ther. 2016;157:120–4.PubMedCrossRef
6.
go back to reference Ettinger DS, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, et al. Non-small cell lung cancer. J Natl Compr Cancer Netw. 2012;10(10):1236–71.CrossRef Ettinger DS, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, et al. Non-small cell lung cancer. J Natl Compr Cancer Netw. 2012;10(10):1236–71.CrossRef
7.
go back to reference O'Flaherty JD, Gray S, Richard D, Fennell D, O'Leary JJ, Blackhall FH, O'Byrne KJ. Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer. Lung Cancer. 2012;76(1):19–25.PubMedCrossRef O'Flaherty JD, Gray S, Richard D, Fennell D, O'Leary JJ, Blackhall FH, O'Byrne KJ. Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer. Lung Cancer. 2012;76(1):19–25.PubMedCrossRef
8.
go back to reference Tartarone A, Rossi E, Lerose R, Mambella G, Calderone G, Zamarchi R, Aieta M. Possible applications of circulating tumor cells in patients with non small cell lung cancer. Lung Cancer. 2017;107:59–64.PubMedCrossRef Tartarone A, Rossi E, Lerose R, Mambella G, Calderone G, Zamarchi R, Aieta M. Possible applications of circulating tumor cells in patients with non small cell lung cancer. Lung Cancer. 2017;107:59–64.PubMedCrossRef
9.
go back to reference Krebs MG, Sloane R, Priest L, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011;29(12):1556–63.PubMedCrossRef Krebs MG, Sloane R, Priest L, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011;29(12):1556–63.PubMedCrossRef
10.
go back to reference Hou JM, Krebs M, Ward T, Sloane R, Priest L, Hughes A, Clack G, Ranson M, Blackhall F, Dive C. Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol. 2011;178(3):989–96.PubMedPubMedCentralCrossRef Hou JM, Krebs M, Ward T, Sloane R, Priest L, Hughes A, Clack G, Ranson M, Blackhall F, Dive C. Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol. 2011;178(3):989–96.PubMedPubMedCentralCrossRef
11.
go back to reference Ksiazkiewicz M, Markiewicz A, Zaczek AJ. Epithelial-mesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiology. 2012;2012(79):195–208.CrossRef Ksiazkiewicz M, Markiewicz A, Zaczek AJ. Epithelial-mesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiology. 2012;2012(79):195–208.CrossRef
12.
go back to reference Raghu K. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest. 2009;119(6):1417–9.CrossRef Raghu K. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest. 2009;119(6):1417–9.CrossRef
13.
go back to reference Liu H, Zhang X, Li J, Sun B, Qian H, Yin Z. The biological and clinical importance of epithelial-mesenchymal transition in circulating tumor cells. J Cancer Res Clin Oncol. 2015;141(2):189–201.PubMedCrossRef Liu H, Zhang X, Li J, Sun B, Qian H, Yin Z. The biological and clinical importance of epithelial-mesenchymal transition in circulating tumor cells. J Cancer Res Clin Oncol. 2015;141(2):189–201.PubMedCrossRef
14.
go back to reference Lowes LE, Allan AL. Circulating tumor cells and implications of the epithelial-to-Mesenchymal transition. Adv Clin Chem. 2018;83:121–81.PubMedCrossRef Lowes LE, Allan AL. Circulating tumor cells and implications of the epithelial-to-Mesenchymal transition. Adv Clin Chem. 2018;83:121–81.PubMedCrossRef
15.
go back to reference Wu S, Liu S, Liu Z, Huang J, Pu X, Li J, Yang D, Deng H, Yang N, Xu J. Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS One. 2015;10(4):e0123976.PubMedPubMedCentralCrossRef Wu S, Liu S, Liu Z, Huang J, Pu X, Li J, Yang D, Deng H, Yang N, Xu J. Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS One. 2015;10(4):e0123976.PubMedPubMedCentralCrossRef
16.
go back to reference Cohen SJ, Punt C, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.PubMedCrossRef Cohen SJ, Punt C, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.PubMedCrossRef
18.
go back to reference Yu N, Zhou J, Cui F, Tang X. Circulating tumor cells in lung cancer: detection methods and clinical applications. Lung. 2015;193(2):157–71.PubMedCrossRef Yu N, Zhou J, Cui F, Tang X. Circulating tumor cells in lung cancer: detection methods and clinical applications. Lung. 2015;193(2):157–71.PubMedCrossRef
19.
go back to reference Adan A, Alizada G, Kiraz Y, Baran Y, Nalbant A. Flow cytometry: basic principles and applications. Crit Rev Biotechnol. 2017;37(2):163–76.PubMedCrossRef Adan A, Alizada G, Kiraz Y, Baran Y, Nalbant A. Flow cytometry: basic principles and applications. Crit Rev Biotechnol. 2017;37(2):163–76.PubMedCrossRef
20.
go back to reference Alix-Panabieres C, Pantel K. Technologies for detection of circulating tumor cells: facts and vision. Lab Chip. 2014;14(1):57–62.PubMedCrossRef Alix-Panabieres C, Pantel K. Technologies for detection of circulating tumor cells: facts and vision. Lab Chip. 2014;14(1):57–62.PubMedCrossRef
21.
go back to reference Chikaishi Y, Yoneda K, Ohnaga T, Tanaka F. EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip. Oncol Rep. 2017;37(1):77–82.PubMedCrossRef Chikaishi Y, Yoneda K, Ohnaga T, Tanaka F. EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip. Oncol Rep. 2017;37(1):77–82.PubMedCrossRef
22.
go back to reference Wu S, Liu S, et al. Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions. Clin Chem Lab Med. 2014;52(2). Wu S, Liu S, et al. Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions. Clin Chem Lab Med. 2014;52(2).
23.
go back to reference Murlidhar V, Reddy RM, Fouladdel S, Zhao L, Ishikawa MK, Grabauskiene S, Zhang Z, Lin J, Chang AC, Carrott P, et al. Poor prognosis indicated by venous circulating tumor cell clusters in early-stage lung cancers. Cancer Res. 2017;77(18):5194–206.PubMedPubMedCentralCrossRef Murlidhar V, Reddy RM, Fouladdel S, Zhao L, Ishikawa MK, Grabauskiene S, Zhang Z, Lin J, Chang AC, Carrott P, et al. Poor prognosis indicated by venous circulating tumor cell clusters in early-stage lung cancers. Cancer Res. 2017;77(18):5194–206.PubMedPubMedCentralCrossRef
24.
go back to reference Liu DG, Xue L, Li J, Yang Q, Peng JZ. Epithelial-mesenchymal transition and GALC expression of circulating tumor cells indicate metastasis and poor prognosis in non-small cell lung cancer. Cancer Biomark. 2018;22(3):417–26.PubMedCrossRef Liu DG, Xue L, Li J, Yang Q, Peng JZ. Epithelial-mesenchymal transition and GALC expression of circulating tumor cells indicate metastasis and poor prognosis in non-small cell lung cancer. Cancer Biomark. 2018;22(3):417–26.PubMedCrossRef
25.
go back to reference Li S, Chen Q, Li H, Wu Y, Feng J, Yan Y. Mesenchymal circulating tumor cells (CTCs) and OCT4 mRNA expression in CTCs for prognosis prediction in patients with non-small-cell lung cancer. Clin Transl Oncol. 2017;19(9):1147–53. Li S, Chen Q, Li H, Wu Y, Feng J, Yan Y. Mesenchymal circulating tumor cells (CTCs) and OCT4 mRNA expression in CTCs for prognosis prediction in patients with non-small-cell lung cancer. Clin Transl Oncol. 2017;19(9):1147–53.
26.
go back to reference Li TT. Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: relevance to therapy response. World J Gastroenterol. 2015;21(47):13259.PubMedPubMedCentralCrossRef Li TT. Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: relevance to therapy response. World J Gastroenterol. 2015;21(47):13259.PubMedPubMedCentralCrossRef
27.
go back to reference Tanaka F, Yoneda K, Kondo N, Hashimoto M, Takuwa T, Matsumoto S, Okumura Y, Rahman S, Tsubota N, Tsujimura T, et al. Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res. 2009;15(22):6980–6.PubMedCrossRef Tanaka F, Yoneda K, Kondo N, Hashimoto M, Takuwa T, Matsumoto S, Okumura Y, Rahman S, Tsubota N, Tsujimura T, et al. Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res. 2009;15(22):6980–6.PubMedCrossRef
28.
go back to reference Li Y, Cheng X, Chen Z, Liu Y, Liu Z, Xu S. Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients. Sci Rep. 2017;7(1):4971.PubMedPubMedCentralCrossRef Li Y, Cheng X, Chen Z, Liu Y, Liu Z, Xu S. Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients. Sci Rep. 2017;7(1):4971.PubMedPubMedCentralCrossRef
Metadata
Title
Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer
Authors
Jingyao Li
Yi Liao
Yaling Ran
Guiyu Wang
Wei Wu
Yang Qiu
Jie Liu
Ningyu Wen
Tao Jing
Haidong Wang
Shixin Zhang
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
NSCLC
NSCLC
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-01314-4

Other articles of this Issue 1/2020

BMC Pulmonary Medicine 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.