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

Alexander Semaan; Vincent Bernard; Dong U Kim; Jaewon J Lee; Jonathan Huang; Nabiollah Kamyabi; Bret M Stephens; Wei Qiao; Gauri R Varadhachary; Matthew H Katz; Yu Shen; Francis Anthony San Lucas; Peter Gascoyne; Hector A Alvarez; Anirban Maitra; Paola A Guerrero

doi:10.1038/s41416-021-01350-9

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

Journal article

Peer reviewed

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

Alexander Semaan, Vincent Bernard, Dong U Kim, Jaewon J Lee, Jonathan Huang, Nabiollah Kamyabi, Bret M Stephens, Wei Qiao, Gauri R Varadhachary, Matthew H Katz, …

British journal of cancer, Vol.124(12), pp.1970-1977

06/08/2021

DOI: 10.1038/s41416-021-01350-9

PMID: 33785875

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Abstract

Limited accessibility of the tumour precludes longitudinal characterisation for therapy guidance in pancreatic ductal adenocarcinoma (PDAC). 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. 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. Our results underscore the importance of immunophenotyping and quantifying specific CTC sub-populations in PDAC.

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

Details

Title: Subtitle: Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer
Creators: Alexander Semaan - The University of Texas MD Anderson Cancer Center
Vincent Bernard - The University of Texas MD Anderson Cancer Center
Dong U Kim - The University of Texas MD Anderson Cancer Center
Jaewon J Lee - The University of Texas MD Anderson Cancer Center
Jonathan Huang - The University of Texas MD Anderson Cancer Center
Nabiollah Kamyabi - The University of Texas MD Anderson Cancer Center
Bret M Stephens - The University of Texas MD Anderson Cancer Center
Wei Qiao - The University of Texas MD Anderson Cancer Center
Gauri R Varadhachary - The University of Texas MD Anderson Cancer Center
Matthew H Katz - The University of Texas MD Anderson Cancer Center
Yu Shen - The University of Texas MD Anderson Cancer Center
Francis Anthony San Lucas - The University of Texas MD Anderson Cancer Center
Peter Gascoyne - Advance Electrofluidic System Ilc, Houston, TX, USA
Hector A Alvarez - The University of Texas MD Anderson Cancer Center
Anirban Maitra - The University of Texas MD Anderson Cancer Center
Paola A Guerrero - The University of Texas MD Anderson Cancer Center
Resource Type: Journal article
Publication Details: British journal of cancer, Vol.124(12), pp.1970-1977
DOI: 10.1038/s41416-021-01350-9
PMID: 33785875
NLM abbreviation: Br J Cancer
ISSN: 0007-0920
eISSN: 1532-1827
Grant note: T32CA009599 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) T32 CA009599 / NCI NIH HHS T32CA217789-03 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA221707 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01 CA196403 / NCI NIH HHS P50 CA221707 / NCI NIH HHS U01 CA200468 / NCI NIH HHS U54 CA096297 / NCI NIH HHS U54CA096297 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) T32 CA217789 / NCI NIH HHS
Language: English
Date published: 06/08/2021
Academic Unit: Surgery
Record Identifier: 9985240895602771

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