Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells
Authors
Carlos A. Aya-Bonilla, Edith Cowan UniversityFollow
Michael Morici, Edith Cowan UniversityFollow
Xin Hong
Ashleigh Cavell McEvoy, Edith Cowan UniversityFollow
Ryan Joseph Sullivan
James Freeman, Edith Cowan University
Leslie Calapre, Edith Cowan UniversityFollow
Muhammad Adnan Khattak, Edith Cowan UniversityFollow
Tarek Meniawy
Michael Millward
Mel Ziman, Edith Cowan UniversityFollow
Elin Solomonovna Gray, Edith Cowan UniversityFollow
Document Type
Journal Article
Publication Title
British Journal of Cancer
Publisher
Springer Nature
School
School of Medical and Health Sciences
RAS ID
31432
Funders
Edith Cowan University, ECU
National Health and Medical Research Council, NHMRC
Grant Number
NHMRC Number : 1013349
Abstract
Background: Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application. Methods: Here we compared two microfluidic devices for the recovery of circulating melanoma cells. The presence of CTCs in 43 blood samples from patients with metastatic melanoma was evaluated using a combination of immunocytochemistry and transcript analyses of five genes by RT-PCR and 19 genes by droplet digital PCR (ddPCR), whereby a CTC score was calculated. Circulating tumour DNA (ctDNA) from the same patient blood sample, was assessed by ddPCR targeting tumour-specific mutations. Results: Our analysis revealed an extraordinary heterogeneity amongst melanoma CTCs, with multiple non-overlapping subpopulations. CTC detection using our multimarker approach was associated with shorter overall and progression-free survival. Finally, we found that CTC scores correlated with plasma ctDNA concentrations and had similar pharmacodynamic changes upon treatment initiation. Conclusions: Despite the high phenotypic and molecular heterogeneity of melanoma CTCs, multimarker derived CTC scores could serve as viable tools for prognostication and treatment response monitoring in patients with metastatic melanoma. © 2020, The Author(s), under exclusive licence to Cancer Research UK.
DOI
10.1038/s41416-020-0750-9
Access Rights
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Comments
Aya-Bonilla, C. A., Morici, M., Hong, X., McEvoy, A. C., Sullivan, R. J., Freeman, J., ... & Ziman, M. (2020). Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells. British Journal of Cancer, 122(7), 1059-1067. https://doi.org/10.1038/s41416-020-0750-9