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Molecular Diagnostics

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

British Journal of Cancer volume 124, pages 1970–1977 (2021)Cite this article

Subjects

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.

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Fig. 1: Capture efficiency of epitope-independent microfluidics device.
Fig. 2: Number of CTCs identified in PDAC patients.
Fig. 3: Comparison of total counts in sub-populations.

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Acknowledgements

Not applicable.

Author information

Author notes

  1. These authors contributed equally: Alexander Semaan, Vincent Bernard, Dong U. Kim

Authors and Affiliations

  1. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Alexander Semaan, Vincent Bernard, Dong U. Kim, Jaewon J. Lee, Jonathan Huang, Nabiollah Kamyabi, Bret M. Stephens, Anirban Maitra & Paola A. Guerrero

  2. Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Alexander Semaan, Vincent Bernard, Dong U. Kim, Jonathan Huang, Nabiollah Kamyabi, Bret M. Stephens, Anirban Maitra & Paola A. Guerrero

  3. Department of Gastroenterology and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea

    Dong U. Kim

  4. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jaewon J. Lee & Matthew H. Katz

  5. Department of Bioengineering, Rice University, Houston, TX, USA

    Nabiollah Kamyabi

  6. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Wei Qiao & Yu Shen

  7. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Gauri R. Varadhachary

  8. Deparment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Francis Anthony San Lucas & Hector A. Alvarez

  9. Advance Electrofluidic System Ilc, Houston, TX, USA

    Peter Gascoyne

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  1. Alexander Semaan
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Contributions

A.M., P.A.G., H.A. Study Design: A.M., P.A.G., H.A., A.S., V.B., D.U.K. Provision of clinical samples and information: B.S., G.R.V., M.H.K. Samples processing: A.S., V.B., P.G., D.U.K. Microfluidics device design: P.G., F.A.S.L. Sample isolation: A.S., V.B., P.A.G., D.U.K., N.K. Samples staining and cytometry: A.S., V.B., P.A.G., D.U.K. Data analysis: J.H., F.A.S.L., J.J.L., W.Q., Y.S. P.A.G. Manuscript writing: A.S., V.B. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Paola A. Guerrero.

Ethics declarations

Ethics approval and consent to participate

The study was performed in accordance with standard ethical guidelines approved by the institutional review board (IRB), protocol numbers PA11-0670 and PA15-0014 at MD Anderson Cancer Center, and in accordance with the Declaration of Helsinki. Patients provided their informed consent to participate in this study.

Data availability

All data generated and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

A.M. receives royalties for a pancreatic cancer biomarker test from Cosmos Wisdom Biotechnology, and this financial relationship is managed and monitored by the UTMDACC Conflict of Interest Committee. A.M. is also listed as an inventor on a patent that has been licensed by Johns Hopkins University to Thrive Earlier Detection. The remaining authors declare no competing interests.

Funding information

This research was supported in part by the Cancer Prevention and Research Institute of Texas (CPRIT) (No. RP160517), NCI P50 CA221707, U01 CA196403 and U01 CA200468 to A.M. N.K. was supported by the CPRIT Research Training Program (No. RP170067). V.B. was supported by the CPRIT Research Training Program (Nos. RP140106 and RP170067) and NCI (Nos. T32CA217789-03 and U54CA096297). J.J.L. was supported by the National Institutes of Health (NIH) (No. T32CA009599). A.S. was supported by the German Research Foundation (SE-2616/2-1). D.U.K. was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2018R1C1B5086234).

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Semaan, A., Bernard, V., Kim, D.U. et al. Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer. Br J Cancer 124, 1970–1977 (2021). https://doi.org/10.1038/s41416-021-01350-9

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