Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells
Menée à partir de 43 échantillons sanguins prélevés sur des patients atteints d'un mélanome métastatique, cette étude évalue l'association entre la détection de cellules tumorales circulantes, à l'aide d'une approche combinant analyse histochimique et analyse transcriptionnelle de 5 gènes par RT-PCR et de 19 gènes par PCR numérique à gouttelettes, et le pronostic
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.
British Journal of Cancer , résumé, 2020