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

Int J Oncol. 2014 Jul;45(1):227-34. doi: 10.3892/ijo.2014.2409. Epub 2014 Apr 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Oncolytic Viruses / genetics*
  • Oncolytic Viruses / metabolism
  • Prospective Studies
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / pathology*
  • Survival Analysis
  • Telomerase / genetics
  • Telomerase / metabolism*

Substances

  • Recombinant Fusion Proteins
  • Telomerase