Clinical Trials Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2019; 25(1): 138-150
Published online Jan 7, 2019. doi: 10.3748/wjg.v25.i1.138
Molecular detection of epithelial-mesenchymal transition markers in circulating tumor cells from pancreatic cancer patients: Potential role in clinical practice
Xiao-Hui Zhao, Zai-Rui Wang, Chang-Long Chen, Ling Di, Zhuo-Fei Bi, Zhi-Hua Li, Yi-Min Liu
Xiao-Hui Zhao, Zai-Rui Wang, Chang-Long Chen, Ling Di, Zhuo-Fei Bi, Zhi-Hua Li, Yi-Min Liu, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Xiao-Hui Zhao, Zai-Rui Wang, Chang-Long Chen, Ling Di, Zhuo-Fei Bi, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Zhi-Hua Li, Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Author contributions: Liu YM, Zhao XH, and Li ZH designed the research, analyzed and interpreted the data, and wrote the paper; Wang ZR and Chen CL analyzed and interpreted the data; Bi ZF, Ding L, and Qing L wrote the paper.
Supported by Guangdong Natural Science Foundation, No. 2016A030313312.
Institutional review board statement: The study protocol was reviewed and approved by Institutional Review Board of Sun Yat-sen Memorial Hospital.
Clinical trial registration statement: The study is registered at www.chictr.org.cn and the registration identification number is chiCTR1800018513.
Informed consent statement: All participants signed an informed consent form prior to study enrollment.
Conflict-of-interest statement: The authors do not have any conflict of interest to disclose.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: We complied with CONSORT 2010 during the period of the study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Yi-Min Liu, MA, Associate Specialist, Professor, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan-Jiang Xi Road, Guangzhou 510120, Guangdong Province, China. liuyimin1995@sina.com
Telephone: +86-13828401190 Fax: +86-21-81332533
Received: October 13, 2018
Peer-review started: October 15, 2018
First decision: November 7, 2018
Revised: December 5, 2018
Accepted: December 6, 2018
Article in press: December 6, 2018
Published online: January 7, 2019
Abstract
AIM

To evaluate the clinical properties of three subpopulations of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) patients.

METHODS

We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule (EpCAM) (E-CTC), the mesenchymal cell markers vimentin and twist (M-CTC), or both (E/M-CTC) using the CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation. CTC enumeration and classification were correlated with patient clinicopathological features and outcomes.

RESULTS

CTCs were detected in 78.5% of PDAC patients. The number of total CTCs ranged from 0 to 26 across all 107 patients, with a median value of six. CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier survival analysis showed that patients with ≥ 6 total CTCs had significantly decreased overall survival and progression-free survival compared with patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage (P < 0.01) and distant metastasis (P < 0.01). Additionally, lymphocyte counts and NLR in patients without CTCs were significantly different from those in patients testing positive for each CTC subpopulation (P < 0.01).

CONCLUSION

Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.

Keywords: Pancreatic ductal adenocarcinoma, Circulating tumor cells, Epithelial-mesenchymal transition, Metastasis, Neutrophil-to-lymphocyte ratio

Core tip: In the present study, circulating tumor cell (CTC) enumeration and classification in pancreatic ductal adenocarcinoma (PDAC) patients were examined using the CanPatrol system. We explored the relationship between CTC status and survival and prognosis in 107 PDAC patients in China. CTC status was correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, neutrophil-to-lymphocyte ratio, and patient prognosis. Our findings demonstrate that CTCs show promise as a prognostic biomarker and provide useful evidence for determining an appropriate clinical approach for pancreatic adenocarcinoma patients.