Prognostic impact of the number of viable circulating cells with high telomerase activity in gastric cancer patients: A prospective study

Ito,Hiroaki; Inoue,Haruhiro; Kimura,Satoshi; Ohmori,Tohru; Ishikawa,Fumihiro; Gohda,Keigo; Sato,Jun

doi:10.3892/ijo.2014.2409

Prognostic impact of the number of viable circulating cells with high telomerase activity in gastric cancer patients: A prospective study

Authors:
- Hiroaki Ito
- Haruhiro Inoue
- Satoshi Kimura
- Tohru Ohmori
- Fumihiro Ishikawa
- Keigo Gohda
- Jun Sato
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Affiliations: Digestive Disease Center, Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama 224-8503, Japan, Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama 224-8503, Japan, Institute of Molecular Oncology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan, Department of Cancer Cell Biology, Showa University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan, Central Research Laboratories, Sysmex Corporation, Nishi-ku, Kobe 651-2271, Japan
Published online on: April 29, 2014 https://doi.org/10.3892/ijo.2014.2409
Pages: 227-234

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Abstract

The identification of circulating tumor cells (CTCs) in peripheral blood is a useful approach to estimate prognosis, monitor disease progression and measure treatment effects in several types of malignancies. We have previously used OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. GFP-positive cells (GFP+ cells) were counted under a fluorescence microscope. Our results showed that the number of at least 7.735 µm in diameter GFP+ cells (L-GFP+ cells) in the peripheral blood was a significant marker of prognosis in gastric cancer patients. However, tumor cells undergoing epithelial-mesenchymal transition (EMT) have been reported to be smaller in size than cells without EMT features; thus, CTCs undergoing EMT may escape detection with this technique. Therefore, in this study, we analyzed the relationship between patient outcome and the number of GFP+ cells of any size. We obtained peripheral blood samples from 65 patients with gastric cancer. After infection of OBP-401, GFP+ cells were counted and measured. The relationship between the number of GFP+ cells and surgical outcome was analyzed. The median follow-up period of the surviving patients was 36 months. A significant difference in overall survival was found between patients with 0-5 and patients with ≥6 L-GFP+ cells. No clear relationship was established between the number of small-sized GFP+ cells and patient prognosis. The number of L-GFP+ cells was significantly related to overall survival in patients with gastric cancer. The detection of L-GFP+ cells using OBP-401 may be a useful prognostic marker in gastric cancer.

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