Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2015; 21(47): 13259-13267
Published online Dec 21, 2015. doi: 10.3748/wjg.v21.i47.13259
Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response
Ting-Ting Li, Hao Liu, Feng-Ping Li, Yan-Feng Hu, Ting-Yu Mou, Tian Lin, Jiang Yu, Lei Zheng, Guo-Xin Li
Ting-Ting Li, Hao Liu, Feng-Ping Li, Yan-Feng Hu, Ting-Yu Mou, Tian Lin, Jiang Yu, Guo-Xin Li, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Lei Zheng, Department of Laboratory Medicine, Sino-UK Circulating Biomarkers’ Exploration and Detection Centre, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: Li TT, Liu H and Yu J contributed equally to this work and should be considered as co-first authors; Li TT, Liu H and Li GX designed the research; Lin T, Mou TY, Hu YF, Yu J and Li GX performed the surgeries and collected the data; Li TT, Li FP and Zheng L performed the experiment; Li TT and Liu H analyzed the data; Li TT, Liu H and Yu J wrote the paper.
Supported by Major Program of Science and Technology Program of Guangzhou, No. 201300000087; Research Fund of Public Welfare in Health Industry of National Health and Family Planning Commission of China, No. 201402015 and No. 201502039; National Key Technology R&D Program, No. 2013BAI05B05; and Key Clinical Specialty Discipline Construction Program.
Institutional review board statement: The study protocol was reviewed and approved by Institutional Review Board of Nanfang Hospital.
Institutional animal care and use committee statement: The present study did not involve animal experiments.
Conflict-of-interest statement: The authors do not have any conflict of interest to disclose.
Data sharing statement: No additional data are available.
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/
Correspondence to: Guo-Xin Li, MD, PhD, FRCS, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, Guangdong Province, China. gzliguoxin@163.com
Telephone: +86-20-61641681 Fax: +86-20-62787626
Received: July 31, 2015
Peer-review started: August 1, 2015
First decision: August 26, 2015
Revised: August 31, 2015
Accepted: October 17, 2015
Article in press: October 20, 2015
Published online: December 21, 2015
Processing time: 137 Days and 2 Hours
Abstract

AIM: To evaluate the epithelial-to-mesenchymal transition (EMT) of circulating tumor cells (CTCs) in gastric cancer patients.

METHODS: We detected tumor cells for expression of four epithelial (E+) transcripts (keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal (M+) transcripts (Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6th cycle of XELOX based chemotherapy (about 6 mo postoperatively)].

RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E+/M+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35 (79.5%) patients at baseline. Five types of cells including from exclusively E+ CTCs to intermediate CTCs and exclusively M+ CTCs were identified (4 patients with M+ CTCs and 10 patients with M+ or M+ > E+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of CanPatrolTM system and the correlation coefficient (R2) was 0.999.

CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.

Keywords: Gastric cancer; Epithelial-to-mesenchymal transition; Circulating tumor cells; Chemotherapy; Therapy response

Core tip: Epithelial-to-mesenchymal transition has been thought to play a critical role in tumor metastatic progression in preclinical models, however, characterizing the epithelial vs mesenchymal phenotypes of circulating tumor cells has been challenging. In this study, we aimed to evaluate epithelial-to-mesenchymal transition phenomenon in circulating gastric tumor cells by a combination of physical and biological methods. Our findings have provided evidence of the phenomenon both in rare cells within primary tumors and more abundantly in circulating tumor cells. Furthermore, we demonstrated that the evaluation of the mesenchymal circulating tumor cells in peripheral blood can be used to monitor therapy response in gastric cancer patients.