School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Br J Cancer. 2020 Mar;122(7):1059-1067. doi: 10.1038/s41416-020-0750-9. Epub 2020 Feb 10.
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.
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.
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.
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.
循环肿瘤细胞（CTC）可通过微创血液样本进行评估，具有作为预测性、预后性和药效动力学生物标志物的潜在用途。黑色素瘤 CTC 的高度异质性阻碍了它们的检测和临床应用。
在这里，我们比较了两种用于回收循环黑色素瘤细胞的微流控装置。通过免疫细胞化学和 RT-PCR 分析五个基因以及 ddPCR 分析 19 个基因的转录分析，结合评估了 43 份转移性黑色素瘤患者血液样本中 CTC 的存在，其中计算了 CTC 评分。通过靶向肿瘤特异性突变的 ddPCR 评估来自同一患者血液样本的循环肿瘤 DNA（ctDNA）。
我们的分析显示黑色素瘤 CTC 之间存在非凡的异质性，具有多个不重叠的亚群。使用我们的多标志物方法检测 CTC 与总生存期和无进展生存期较短相关。最后，我们发现 CTC 评分与血浆 ctDNA 浓度相关，并在治疗开始时具有相似的药效动力学变化。
尽管黑色素瘤 CTC 具有高度的表型和分子异质性，但多标志物衍生的 CTC 评分可作为预测和监测转移性黑色素瘤患者治疗反应的可行工具。
