随着肿瘤诊疗越来越个体化、精准化,循环肿瘤细胞检测技术由于其创伤小、可重复性高,对肿瘤预后评估、指导治疗用药、研究肿瘤生物学特性等方面存在着巨大的应用价值。然而,由于循环肿瘤细胞在外周血中含量少、检出率低,且检测成本高,从而限制了检测技术的发展。本篇文章对现有多种循环肿瘤细胞检测方法进行综述,希望能对探索更高效的检测方式有所启发。
With more and more individualized and precise diagnosis and treatment of tumors, the detection technology of circulating tumor cells has great application value for prognosis assessment, guiding treatment and medication, and studying biological characteristics of tumors, due to its small trauma and high repeatability. However, due to the low content of circulating tumor cells in pe-ripheral blood, low detection rate and high detection cost, the development of detection technology has been limited. This paper reviews the current methods of detecting circulating tumor cells, hoping to inspire us to explore more efficient methods.
循环肿瘤细胞,结直肠癌,检测技术,综述, Circulating Tumor Cell Colorectal Cancer Detection Technology Review循环肿瘤细胞检测方法以及临床应用的研究 进展
根据CTC与血细胞的细胞密度、体积大小、细胞刚性以及电性能等物理性质方面的差异可以从外周血中进行CTC富集,其中最常用的有根据CTC密度低于血细胞而使用的密度梯度离心法与根据CTC直径大于血细胞而使用的膜滤过分离法(isolation by size of epithelial tumorcells, ISET) [6]。此外,由于CTC具有更大的细胞总表面积,导致CTC的膜电容较高,有学者通过双向电泳法分离CTC [7]。也有学者发现CTC具有更高的质核比,通过筛选具有高质核比特征的细胞进行CTC富集 [8]。基于物理性质的富集方法的优点是操作简便、价格低、对CTC活性影响小以及便于进行下游分析。同时,由于物理富集法无需抗体标记细胞,可以避免只分离带有特定免疫标识的CTC,从而使得到的CTC种类更全面。但是,对于一些物理特性与血细胞相似的CTC难以达到分离效果,且由于没有特异的肿瘤学标志物,虽然避免了遗漏,却导致分离得到的CTC不纯,计数难度大。
徐士伟,尹 东. 循环肿瘤细胞检测方法以及临床应用的研究进展 The Research Progress of Circulating Tumor Cell Detection and Clinical Application[J]. 临床医学进展, 2018, 08(10): 958-962. https://doi.org/10.12677/ACM.2018.810159
参考文献ReferencesHaber, D.A., Gray, N.S. and Baselga, J. (2011) The Evolving War on Cancer. Cell, 145, 19-24. <br>https://doi.org/10.1016/j.cell.2011.03.026Krebs, M.G., Metcalf, R.L., Carter, L., Brady, G., Blackhall, F.H. and Dive, C. (2014) Molecular Analysis of Circulating Tumour Cells-Biology and Biomarkers. Nature Reviews Clinical Oncology, 11, 129-144. <br>https://doi.org/10.1038/nrclinonc.2013.253郭玮, 孙云帆, 潘柏申, 等. 循环肿瘤细胞检测及临床应用价值[J]. 中华临床实验室管理电子杂志, 2014, 82(3): 43-48.Chen, F.F., Wang, S.Y., Fang, Y., et al. (2016) Feasibility of a Novel One-Stop ISET Device to Capture CTCs and Its Clinical Application. Oncotarget, 8.余锋, 张妤, 施乐华, 殷正丰. 循环肿瘤细胞检测的临床应用[J]. 世界华人消化杂志, 2010, 18(22): 2346-2349.Gascoyne, P.R., Noshari, J., Anderson, T.J. and Becker, F.F. (2009) Isolation of Rare Cells from Cell Mixtures by Dielectrophoresis. Electrophoresis, 30, 1388-1398. <br>https://doi.org/10.1002/elps.200800373Liu, Z.X., Guo, W.X., Zhang, D.D., et al. (2016) Circulating Tumor Cell Detection in Hepatocellular Carcinoma Based on Karyoplasmic Ratios Using Imaging Flow Cytometry. Scientific Reports, 6, Article Number: 39808. <br>https://doi.org/10.1038/srep39808Hyun, K.A., Lee, T.Y. and Jung, H.I. (2013) Negative Enrichment of Circulating Tumor Cells Using a Geometrically Activated Surface Interaction Chip. Analytical Chemistry, 85, 4439-4445. <br>https://doi.org/10.1021/ac3037766王东升, 张岩, 吕平, 朱晓辉, 张玲, 周芳, 高晓明. 抗体包被免疫磁珠的研制及其应用[J]. 细胞与分子免疫学杂志, 2001, 17(3): 296-297.Saucedo, Z.N., Mewes, S., Niestroj, R.A., et al. (2012) A Novel Method for the in Vivo Isolation of Circulating Tumor Cells from Peripheral Blood of Cancer Patients Using a Functionalized and Structured Medical Wire. International Journal of Oacology, 41, 1241-1250.Lowes Lori, E., Goodale, D., Xia, Y., et al. (2016) Epithelial-to-Mesenchymal Transition Leads to Disease-Stage Differences in Circulating Tumor Cell Detection and Metastasis in Pre-Clinical Models of Prostate Cancer. Oncotarget, 76.Ning, Y., Hanna Diana, L., Zhang, W., et al. (2015) Cytokeratin-20 and Survivin-Expressing Circulating Tumor Cells Predict Survival in Metastatic Colorectal Cancer Patients by a Combined Immunomagnetic qRT-PCR Approach. Molecular Cancer Therapeutics, 14, 2401-2418. <br>https://doi.org/10.1158/1535-7163.MCT-15-0359Santana Steven, M., Liu, H., Bander Neil, H., et al. (2012) Immunocapture of Prostate Cancer Cells by Use of Anti-PSMA Antibodies in Microdevices. Biomedical Microdevices, 14, 401-407. <br>https://doi.org/10.1007/s10544-011-9616-5Hyun Kyung, A., Lee, T.Y., Lee, S.H., et al. (2015) Two-Stage Microfluidic Chip for Selective Isolation of Circulating Tumor Cells (CTCs). Biosensors and Bioelectronics, 67, 86-92. <br>https://doi.org/10.1016/j.bios.2014.07.019Nagrath, S., Sequist Lecia, V., Maheswaran, S., et al. (2007) Isolation of Rare Circulating Tumour Cells in Cancer Patients by Microchip Technology. Nature, 450, 1235-1239. <br>https://doi.org/10.1038/nature06385Stott, S.L., et al. (2010) Isolation of Circulating Tumor Cells Using a Microvortex-Generating Herringbone-Chip. Proceedings of the National Academy of Sciences of the United States, 107, 18392-18397. <br>https://doi.org/10.1073/pnas.1012539107Karabacak, N.M., Spuhler, P.S., Fachin, F., et al. (2014) Micro-fluidic, Marker-Free Isolation of Circulating Tumor Cells from Blood Samples. Nature Protocols, 9, 694-710. <br>https://doi.org/10.1038/nprot.2014.044Fatih, S.A., Nicola, A., Nikola, K., et al. (2015) A Microfluidic De-vice for Label-Free, Physical Capture of Circulating Tumor Cell Clusters. Nature Methods, 12, 685-691. <br>https://doi.org/10.1038/nmeth.3404Casavant, B.P., Mosher, R., Warrick, J.W., et al. (2013) A Negative Selection Methodology Using a Microfluidic Platform for the Isolation and Enumeration of Circulating Tumor Cells. Methods, 64, 137-143. <br>https://doi.org/10.1016/j.ymeth.2013.05.027Dent, B.M., Ogle, L.F., O’Donnell, R.L., et al. (2016) High-Resolution Imaging for the Detection and Characterisation of Circulating Tumour Cells from Patients with Oe-sophageal, Hepatocellular, Thyroid and Ovarian Cancers. International Journal of Cancer, 138, 206-216. <br>https://doi.org/10.1002/ijc.29680López-Riquelme, N., Minguela, A., Villar-Permuy, F., et al. (2013) Imaging Cytometry for Counting Circulating Tumor Cells: Comparative Analysis of the CellSearch vs. ImageStream Systems. APMIS, 121, 1139-1143. <br>https://doi.org/10.1111/apm.12061Nieva, J., Wendel, M., Luttgen, M.S., et al. (2012) High-Definition Im-aging of Circulating Tumor Cells and Associated Cellular Events in Non-Small Cell Lung Cancer Patients: A Longitu-dinal Analysis. Physical Biology, 9, Article ID: 016004. <br>https://doi.org/10.1088/1478-3975/9/1/016004Somlo, G., Lau, S.K., Frankel, P., et al. (2011) Multiple Biomarker Expression on Circulating Tumor Cells in Comparison to Tumor Tissues from Primary and Metastatic Sites in Patients with Locally Advanced/Inflammatory, and Stage IV Breast Cancer, Using a Novel Detection Technology. Breast Cancer Research and Treatment, 128, 155-163. <br>https://doi.org/10.1007/s10549-011-1508-0Thore, H., Peer, H., Ann-Britt, N., et al. (2015) In Vitro Detec-tion of Circulating Tumor Cells Compared by the CytoTrack and CellSearch Methods. Tumor Biology, 36, 4597-4601. <br>https://doi.org/10.1007/s13277-015-3105-zAlix-Panabières, C. (2012) EPISPOT Assay: Detection of Viable DTCs/CTCs in Solid Tumor Patients. Recent Results in Cancer Research, 195, 69-76. <br>https://doi.org/10.1007/978-3-642-28160-0_6Nicola, A., Aditya, B., Miyamoto, D.T., et al. (2014) Circu-lating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis. Cell, 158, 1110-1122. <br>https://doi.org/10.1016/j.cell.2014.07.013