Clinical and Translational Research
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Apr 26, 2021; 9(12): 2721-2730
Published online Apr 26, 2021. doi: 10.12998/wjcc.v9.i12.2721
Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer
Sha-Sha Jiang, Chun-Guo Mao, Yong-Geng Feng, Bin Jiang, Shao-Lin Tao, Qun-You Tan, Bo Deng
Sha-Sha Jiang, Chun-Guo Mao, Yong-Geng Feng, Bin Jiang, Shao-Lin Tao, Qun-You Tan, Bo Deng, Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China
Author contributions: Jiang SS and Mao CG performed the research and wrote the paper; Feng YG and Jiang B designed the research and supervised the study; Tao SL and Tan QY designed the research and contributed to the analyses; Deng B provided clinical advice and supervised the report.
Supported by National Natural Science Foundation of China, No. 81572285; The Natural Science Foundation of Chongqing City, No. cstc2018jcyjAX0592; and The Army Medical University Clinical Medical Research Talent Training Program, No. 2018XLC3062.
Institutional review board statement: The study protocol was reviewed and approved by the Ethics Committee of Daping Hospital, Army Medical University 2019, No. 183.
Clinical trial registration statement: This study is registered at https://clinicaltrials.gov/. The registration identification number is NCT02951897.
Informed consent statement: All patients who agreed to participate in the study signed an informed consent.
Conflict-of-interest statement: The authors declare that they have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bo Deng, MD, PhD, Professor, Surgeon, Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Army Medical University, No. 10 Changjiang Branch Street, Yuzhong District, Chongqing 400042, China. dengbo@tmmu.edu.cn
Received: November 20, 2020
Peer-review started: November 20, 2020
First decision: February 12, 2021
Revised: February 19, 2021
Accepted: March 4, 2021
Article in press: March 4, 2021
Published online: April 26, 2021
Abstract
BACKGROUND

Circulating tumor cells (CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition (EMT) markers: CTCs with epithelial markers (E-CTCs), CTCs with mesenchymal markers (M-CTCs), and CTCs with both markers (E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer (LC).

AIM

To clarify the diagnostic value of CTCs categorized by EMT markers in LC.

METHODS

The study included 106 patients with lung adenocarcinoma, including 42 ground-glass opacities (GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrolTM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic (ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques.

RESULTS

Of the 106 LC cases, 94 (89.6%) had at least one CTC. CTCs were detectable in 35 (83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of M-CTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients (80.95% for GGO patients) and the specificity was 78.57%. The Kappa value was 0.415, indicating relative consistency between CanPatrolTM and CytoploRare.

CONCLUSION

CTC detection is valuable for distinguishing LC from controls, and particularly E&M-CTC detection warrants further study.

Keywords: Circulating tumor cells, Epithelial-to-mesenchymal transition, Diagnosis, Lung cancer, Ground-glass opacities, CanPatrol

Core Tip: Circulating tumor cells (CTCs) with epithelial markers (E-CTCs), CTCs with mesenchymal markers (M-CTCs), and CTCs with both markers (E&M-CTCs) are three subtypes of CTCs. Detection of E&M-CTCs have good diagnostic value for distinguishing lung cancer from controls.