Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients

Oncotarget. 2017 May 23;8(21):34884-34895. doi: 10.18632/oncotarget.16818.


Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of non-small cell lung cancer (NSCLC) using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase-specific replication-selective adenovirus (OBP-1101), TelomeScan F35. Peripheral venous blood samples and clinicopathological data were collected from 123 NSCLC patients. The sensitivity of CTC detection was 69.1%, and for patients with stage I, II, III and IV, it was 59.6%, 40.0%, 85.7%, and 75.0%, respectively. Among the EMT-CTC samples, 46% were vimentin positive and 39.0% of non-EMT-CTC samples were EpCAM positive. Patients testing positive for EMT-CTCs at baseline had poor response to chemotherapy (P = 0.025) and decreased progression-free survival (EMT-CTC positive vs. negative: 193 ± 47 days vs. 388 ± 47. days, P = 0.040) in comparison to those testing negative. TelomeScan F35 is a highly sensitive CTC detection system and will be a useful screening tool for early diagnosis of NSCLC patients. Mesenchymal-phenotype CTCs are crucial indicators of chemotherapeutic efficacy in NSCLC patients.

Keywords: EMT; EpCAM; circulating tumor cells; non-small cell lung cancer; telomescan.

MeSH terms

  • A549 Cells
  • Adenoviridae / physiology
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Disease-Free Survival
  • Epithelial Cell Adhesion Molecule / metabolism
  • Epithelial-Mesenchymal Transition
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Prognosis
  • Survival Analysis
  • Telomerase / metabolism*
  • Vimentin / metabolism
  • Virus Replication


  • Epithelial Cell Adhesion Molecule
  • Vimentin
  • Telomerase