Long-term prognostic impact of circulating tumour cells in gastric cancer patients

doi:10.3748/wjg.v22.i46.10232

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World Journal of Gastroenterology

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World J Gastroenterol. Dec 14, 2016; 22(46): 10232-10241
Published online Dec 14, 2016. doi: 10.3748/wjg.v22.i46.10232

Long-term prognostic impact of circulating tumour cells in gastric cancer patients

Hiroaki Ito, Jun Sato, Yukio Tsujino, Noriko Yamaguchi, Satoshi Kimura, Keigo Gohda, Katsuhiro Murakami, Manabu Onimaru, Tohru Ohmori, Fumihiro Ishikawa, Haruhiro Inoue

Hiroaki Ito, Manabu Onimaru, Haruhiro Inoue, Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan

Jun Sato, Yukio Tsujino, Keigo Gohda, Katsuhiro Murakami, Central Research Laboratories, Sysmex Corporation, Kobe 651-2271, Japan

Noriko Yamaguchi, Department of Surgery, Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan

Satoshi Kimura, Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan

Tohru Ohmori, Institute of Molecular Oncology, Showa University School of Medicine, Tokyo 142-8555, Japan

Fumihiro Ishikawa, Department of Cancer Cell Biology, Showa University School of Pharmacy, Tokyo 142-8555, Japan

Author contributions: Ito H conceived and designed the experiments, collected blood samples, performed the experiments, managed clinical examination, performed treatment of individual patients, delivered clinical data, and performed the statistical analysis and data interpretation; Sato J, Tsujino Y, Gohda K, and Murakami K analysed the blood cells in the peripheral blood samples from the patients; Yamaguchi N and Onimaru M managed clinical examination, performed treatment of individual patients, and delivered clinical data; Kimura S participated in the study design, maintained the equipment, including the test tubes, and performed data interpretation; Ohmori T and Ishikawa F participated in the study design and performed data interpretation; Inoue H participated in the study design, performed treatment of individual patients, and performed data interpretation; all authors have read and approved the final manuscript.

Supported by a Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Challenging Exploratory Research (in part), No. 23659308; and JSPS KAKENHI Grant-in-Aid for Scientific Research, No. 26460688.

Institutional review board statement: The study was approved by the Institutional Review Board of the Showa University, Northern Yokohama Hospital (No. 0903-03).

Clinical trial registration statement: This study was registered with the University Hospital Medical Information Network in Japan, UMIN000004026.

Informed consent statement: The study protocol was explained to the patients and volunteers before written informed consent was obtained.

Conflict-of-interest statement: The authors declare that they have no competing interests.

Data sharing statement: No additional data are available.

Correspondence to: Hiroaki Ito, MD, Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-ku, Tokyo 135-8577, Japan. h.ito@med.showa-u.ac.jp

Telephone: +81-3-62046000 Fax: +81-3-62046396

Received: August 19, 2016
Peer-review started: August 22, 2016
First decision: September 12, 2016
Revised: September 27, 2016
Accepted: October 27, 2016
Article in press: October 27, 2016
Published online: December 14, 2016
Processing time: 115 Days and 5.7 Hours

Abstract

AIM

To analyse the long-term prognostic impact of circulating tumour cells (CTCs) in gastric cancer patients who underwent surgery.

METHODS

A 7.5-mL peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated.

RESULTS

The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-mL of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant (P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs (P = 0.034).

CONCLUSION

A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.

Keywords: Circulating tumour cells; Gastric cancer; Surgery; Telomerase; Prognosis

Core tip: We show the long-term prognostic impact of circulating tumour cells (CTCs) in 65 patients with gastric cancer in this report. OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. A lower number of CTCs was correlated with higher relapse-free survival rates in patients with gastric cancer.