Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer

Br J Cancer. 2021 Jun;124(12):1970-1977. doi: 10.1038/s41416-021-01350-9. Epub 2021 Mar 30.

Abstract

Background: Limited accessibility of the tumour precludes longitudinal characterisation for therapy guidance in pancreatic ductal adenocarcinoma (PDAC).

Methods: We utilised dielectrophoresis-field flow fractionation (DEP-FFF) to isolate circulating tumour cells (CTCs) in 272 blood draws from 74 PDAC patients (41 localised, 33 metastatic) to non-invasively monitor disease progression.

Results: Analysis using multiplex imaging flow cytometry revealed four distinct sub-populations of CTCs: epithelial (E-CTC), mesenchymal (M-CTC), partial epithelial-mesenchymal transition (pEMT-CTC) and stem cell-like (SC-CTC). Overall, CTC detection rate was 76.8% (209/272 draws) and total CTC counts did not correlate with any clinicopathological variables. However, the proportion of pEMT-CTCs (prop-pEMT) was correlated with advanced disease, worse progression-free and overall survival in all patients, and earlier recurrence after resection.

Conclusion: Our results underscore the importance of immunophenotyping and quantifying specific CTC sub-populations in PDAC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Pharmacological / analysis
  • Biomarkers, Pharmacological / blood
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • Carcinoma, Pancreatic Ductal / blood
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cells, Cultured
  • Disease Progression
  • Drug Monitoring / methods
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Immunophenotyping
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / classification
  • Neoplastic Cells, Circulating / pathology*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / pathology*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor