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循环肿瘤细胞检测与 Merkel 细胞癌中的多瘤病毒状态。

Circulating Tumor Cell Detection and Polyomavirus Status in Merkel Cell Carcinoma.

机构信息

Laboratory of Rare Human Circulating Cells, University Medical Centre of Montpellier, 34093, Montpellier, France.

Pathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, University Medical Centre, 34090, Montpellier, France.

出版信息

Sci Rep. 2020 Jan 31;10(1):1612. doi: 10.1038/s41598-020-58572-9.

Abstract

The incidence of Merkel cell carcinoma (MCC), a rare and highly metastatic skin malignancy, has sharply increased in the last decade. Clinical biomarkers are urgently needed for MCC prognosis, treatment response monitoring, and early diagnosis of relapse. The clinical interest of circulating tumors cells (CTCs) has been validated in many solid cancers. The aim of this study was to compare CTC detection and characterization in blood samples of patients with MCC using the CellSearch System and the RosetteSep -DEPArray workflow, an innovative procedure to enrich, detect and isolate single CTCs. In preliminary experiments (using spiked MCC cell lines) both methods allowed detecting very few MCC cells. In blood samples from 19 patients with MCC at different stages, CellSearch detected MCC CTCs in 26% of patients, and the R-D workflow in 42% of patients. The detection of CTC-positive patients increased to 52% by the cumulative positivity rate of both methodologies. Moreover, Merkel cell polyomavirus DNA, involved in MCC oncogenesis, was detected in tumor biopsies, but not in all single CTCs from the same patient, reflecting the tumor heterogeneity. Our data demonstrate the possibility to detect, isolate and characterize CTCs in patients with MCC using two complementary approaches.

摘要

Merkel 细胞癌 (MCC) 的发病率在过去十年中急剧上升,MCC 是一种罕见且高度转移性的皮肤恶性肿瘤。目前迫切需要临床生物标志物来预测 MCC 预后、监测治疗反应以及早期诊断复发。循环肿瘤细胞 (CTC) 在许多实体瘤中的临床应用价值已得到验证。本研究旨在比较 CellSearch 系统和 RosetteSep -DEPArray 工作流程(一种用于富集、检测和分离单个 CTC 的创新方法)在检测和表征 MCC 患者血液样本中的 CTC 方面的差异。在初步实验(使用添加了 MCC 细胞系的血液样本)中,两种方法均能检测到极少数 MCC 细胞。在处于不同阶段的 19 名 MCC 患者的血液样本中,CellSearch 检测到 26%的患者存在 MCC CTC,而 R-D 工作流程检测到 42%的患者存在 MCC CTC。通过两种方法的累积阳性率,检测到 CTC 阳性的患者比例增加到 52%。此外,与 MCC 发生相关的 Merkel 细胞多瘤病毒 DNA 存在于肿瘤活检中,但并非来自同一患者的所有单个 CTC 中,这反映了肿瘤的异质性。我们的数据证明了使用两种互补方法在 MCC 患者中检测、分离和表征 CTC 的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9764/6994658/e65d77bd34fe/41598_2020_58572_Fig1_HTML.jpg

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