Prognostic impact of the number of viable circulating cells with high telomerase activity in gastric cancer patients: a prospective study.
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.
Digestive Disease Center, Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama 224-8503, Japan.
Hiroaki
H
Ito
Digestive Disease Center, Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama 224-8503, Japan.
Haruhiro
H
Inoue
Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama 224-8503, Japan.
Satoshi
S
Kimura
Institute of Molecular Oncology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan.
Tohru
T
Ohmori
Department of Cancer Cell Biology, Showa University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan.
Fumihiro
F
Ishikawa
Central Research Laboratories, Sysmex Corporation, Nishi-ku, Kobe 651-2271, Japan.
Keigo
K
Gohda
Central Research Laboratories, Sysmex Corporation, Nishi-ku, Kobe 651-2271, Japan.
Jun
J
Sato
D000328:Adult; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D019098:Telomerase