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

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

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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.

Original language	English (US)
Pages (from-to)	1970-1977
Number of pages	8
Journal	British journal of cancer
Volume	124
Issue number	12
DOIs	https://doi.org/10.1038/s41416-021-01350-9
State	Published - Jun 8 2021

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group

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10.1038/s41416-021-01350-9

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Semaan, A., Bernard, V., Kim, D. U., Lee, J. J., Huang, J., Kamyabi, N., Stephens, B. M., Qiao, W., Varadhachary, G. R., Katz, M. H., Shen, Y., San Lucas, F. A., Gascoyne, P., Alvarez, H. A., Maitra, A., & Guerrero, P. A. (2021). Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer. British journal of cancer, 124(12), 1970-1977. https://doi.org/10.1038/s41416-021-01350-9

Semaan, A, Bernard, V, Kim, DU, Lee, JJ, Huang, J, Kamyabi, N, Stephens, BM, Qiao, W, Varadhachary, GR, Katz, MH , Shen, Y , San Lucas, FA, Gascoyne, P, Alvarez, HA, Maitra, A & Guerrero, PA 2021, 'Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer', British journal of cancer, vol. 124, no. 12, pp. 1970-1977. https://doi.org/10.1038/s41416-021-01350-9

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Cancer Research UK.",

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doi = "10.1038/s41416-021-01350-9",

language = "English (US)",

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T1 - Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer

AU - Semaan, Alexander

AU - Bernard, Vincent

AU - Kim, Dong U.

AU - Lee, Jaewon J.

AU - Huang, Jonathan

AU - Kamyabi, Nabiollah

AU - Stephens, Bret M.

AU - Qiao, Wei

AU - Varadhachary, Gauri R.

AU - Katz, Matthew H.

AU - Shen, Yu

AU - San Lucas, Francis Anthony

AU - Gascoyne, Peter

AU - Alvarez, Hector A.

AU - Maitra, Anirban

AU - Guerrero, Paola A.

PY - 2021/6/8

Y1 - 2021/6/8

N2 - 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.

AB - 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.

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

Abstract

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MD Anderson CCSG core facilities

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