Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients.
Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients.
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DOI：
10.1038/bjc.2012.137
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发表时间：
2012-05-22
影响因子：
8.8
通讯作者：
Coombes, R. C.
中科院分区：
文献类型：
--
作者：
Payne, R. E.;Wang, F.;Su, N.;Krell, J.;Zebrowski, A.;Yaguee, E.;Ma, X-J;Luo, Y.;Coombes, R. C.
目前用于检测血液中的循环肿瘤细胞（CTC）的方法依赖于CTC富集，并且基于CTC上的表面上皮标志物或基于细胞大小差异。本研究的目的是开发和验证一种超灵敏的多重荧光RNA原位杂交（ISH）为基础的CTC检测系统，称为CTC镜。该方法在血液中的单细胞水平上检测多种肿瘤特异性标志物。将掺入肿瘤细胞系的健康血液样本用作CTC scope开发和初始表征的模型系统。为了证明患者血液中CTC检测的可行性，从45名转移性乳腺癌患者中抽取一式两份血液样品，用于通过CTCscope和CellSearch系统进行分析。评估了CTC与肿瘤标志物CA 15 -3和无进展生存期（PFS）的相关性。CTCscope检测了八种上皮标志物和三种上皮间质转化（EMT）标志物的CTC转录本，以提高灵敏度。使用CTCscope检测具有最小富集的CTC，并且未检测到凋亡或死亡细胞。在患者血液样本中，CellSearch检测到的CTC（而非CTCscope）与CA 15 -3水平呈正相关。通过CTC scope或CellSearch检测的循环肿瘤细胞预测PFS（CTC scope，HR（风险比）2.26，95% CI 1.18-4.35，P=0.014; CellSearch，HR 2.50，95% CI 1.27-4.90，P=0.008）。CTCscope比现有的CTC检测方法具有独特的优势。通过仅计数和表征有活力的CTC，CTCscope在治疗监测中提供了额外的预后和预测信息。
Current approaches for detecting circulating tumour cells (CTCs) in blood are dependent on CTC enrichment and are based either on surface epithelial markers on CTCs or on cell size differences. The objectives of this study were to develop and characterise an ultrasensitive multiplex fluorescent RNA in situ hybridisation (ISH)-based CTC detection system called CTCscope. This method detects a multitude of tumour-specific markers at single-cell level in blood. Healthy blood samples spiked with tumour cell lines were used as a model system for the development and initial characterisation of CTCscope. To demonstrate the feasibility of CTC detection in patient blood, duplicate blood samples were drawn from 45 metastatic breast cancer patients for analysis by CTCscope and the CellSearch system. The association of CTCs with the tumour marker CA15-3 and progression-free survival (PFS) were assessed. CTCscope detected CTC transcripts of eight epithelial markers and three epithelial-mesenchymal-transition (EMT) markers for increased sensitivity. CTCscope was used to detect CTCs with minimal enrichment, and did not detect apoptotic or dead cells. In patient blood samples, CTCs detected by CellSearch, but not CTCscope, were positively correlated with CA15-3 levels. Circulating tumour cells detected by either CTCscope or CellSearch predicted PFS (CTCscope, HR (hazard ratio) 2.26, 95% CI 1.18–4.35, P=0.014; CellSearch, HR 2.50, 95% CI 1.27–4.90, P=0.008). CTCscope offers unique advantages over existing CTC detection approaches. By enumerating and characterising only viable CTCs, CTCscope provides additional prognostic and predictive information in therapy monitoring.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
17.1
作者：
Stott SL;Lee RJ;Nagrath S;Yu M;Miyamoto DT;Ulkus L;Inserra EJ;Ulman M;Springer S;Nakamura Z;Moore AL;Tsukrov DI;Kempner ME;Dahl DM;Wu CL;Iafrate AJ;Smith MR;Tompkins RG;Sequist LV;Toner M;Haber DA;Maheswaran S
通讯作者：
Maheswaran S
影响因子：
64.5
作者：
Yang, J;Mani, SA;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
11.5
作者：
Riethdorf, Sabine;Fritsche, Herbert;Pantel, Klaus
通讯作者：
Pantel, Klaus
影响因子：
45.3
作者：
Smith, BM;Slade, MJ;Coombes, RC
通讯作者：
Coombes, RC