循环肿瘤细胞 ： Circulating Tumor Cell

顾名思义，循环肿瘤细胞(CTCs)是肿瘤患者外周血中罕见的细胞。它们已被证明是许多癌症类型中有用的预后标记。在过去的十年里，人们发展了各种方法来检测癌症病人液体活检中的稀有细胞。这些方法揭示了CTCs的表型多样性，以及它们如何代表肿瘤中发现的补体细胞。单细胞蛋白质基因组学已经成为CTC研究的新一代技术方法。

CTC或许可以作为一种marker来标记特定的肿瘤：

有各种各样的仪器和方法来捕获、富集和计数ctc。一旦分离，CTCs可以使用下一代测序(NGS)进行研究，以获得其基因组图谱。使用基于扩增子的NGS面板对CTCs进行定向测序是一种理想的方法，因为该工作流程易于实现，并且只需少量的DNA输入。

对于这种本来就很少的细胞，高通量的优势在哪呢？ 需要先富集在测序。它有marker 吗？ 我测的血液样本里面有CTC吗？如何把他们识别不胡来呢？

Epithelial-marker based approaches are the most widely applied strategies for CTC detection. Among all the platforms, CellSearch from Janssen Diagnostics is considered the most successful. CellSearch is the only FDA-approved platform for CTC detection in clinical practice on patients with breast, prostate, and colorectal cancers. The practicability of CellSearch has been widely verified by many studies and referred as the “golden standard” for evaluating newly developed approaches22. CellSearch uses magnetic beads coupled with anti-EpCAM antibodies at the initial step to enrich EpCAM-positive epithelial cells and later stain the enriched cells for Cytokeratin (CK), CD45, and nucleus (DAPI) to capture CTCs (CK+CD45-DAPI+)and remove leukocytes (CK-CD45+DAPI+).

The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC- patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC-.

More specifically, CTC expresses epithelial markers like epithelial cell adhesion molecules (EpCAM)and Cytokeratin (CK) to variable degrees, but not CD45, a differential marker for while blood cells(WBCs)

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https://blog.crownbio.com/ctc-metastasis-mouse-models
https://pubmed.ncbi.nlm.nih.gov/30649733/
https://www.mdpi.com/2072-6694/12/1/160/htm
https://pubmed.ncbi.nlm.nih.gov/28778937/
https://www.paragongenomics.com/applications/oncology/single_cell_ctc-analysis/#:~:text=Genomic%20Profiling%20of%20Single%20Circulating%20Tumor%20Cell%20%28CTC%29,and%20even%20from%20a%20disseminated%20tumor%20cell%20reservoir.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607822/