Heterogeneity of Circulating Tumor Cell Neoplastic Subpopulations Outlined by Single-Cell Transcriptomics.
Heterogeneity of Circulating Tumor Cell Neoplastic Subpopulations Outlined by Single-Cell Transcriptomics.
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DOI：
10.3390/cancers13194885
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发表时间：
2021-09-29
期刊：
影响因子：
5.2
通讯作者：
Marchetti D
中科院分区：
文献类型：
--
作者：
Pauken CM;Kenney SR;Brayer KJ;Guo Y;Brown-Glaberman UA;Marchetti D
Over 12% of women in the United States will be diagnosed with breast cancer in their lifetime. The overall 5-year survival rate for breast cancer is 90%, but the 5-year survival rate for women diagnosed with metastatic breast cancer is 28.1%. This study aims to characterize the cancerous cells that have left the primary tumor site and entered the blood, known as circulating tumor cells (CTCs). These cells could adhere to a site distant from the tumor and initiate metastasis. CTCs in breast cancer patients’ blood samples were enumerated and imaged. Cells from the blood were collected, RNA extracted, and the gene expression patterns of CTCs and other cell populations in the blood were investigated at the population and single cell level. This is a crucial step in characterizing CTCs as seeds of metastasis in breast cancer and for developing methods of detection to intercept metastasis before it localizes to distant regions of the body. Fatal metastasis occurs when circulating tumor cells (CTCs) disperse through the blood to initiate a new tumor at specific sites distant from the primary tumor. CTCs have been classically defined as nucleated cells positive for epithelial cell adhesion molecule and select cytokeratins (EpCAM/CK/DAPI), while negative for the common lymphocyte marker CD45. The enumeration of CTCs allows an estimation of the overall metastatic burden in breast cancer patients, but challenges regarding CTC heterogeneity and metastatic propensities persist, and their decryption could improve therapies. CTCs from metastatic breast cancer (mBC) patients were captured using the RareCyteTM Cytefinder II platform. The Lin− and Lin+ (CD45+) cell populations isolated from the blood of three of these mBC patients were analyzed by single-cell transcriptomic methods, which identified a variety of immune cell populations and a cluster of cells with a distinct gene expression signature, which includes both cells expressing EpCAM/CK (“classic” CTCs) and cells possessing an array of genes not previously associated with CTCs. This study put forward notions that the identification of these genes and their interactions will promote novel areas of analysis by dissecting properties underlying CTC survival, proliferation, and interaction with circulatory immune cells. It improves upon capabilities to measure and interfere with CTCs for impactful therapeutic interventions.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
--
作者：
Frerich CA;Brayer KJ;Painter BM;Kang H;Mitani Y;El-Naggar AK;Ness SA
通讯作者：
Ness SA
影响因子：
5.2
作者：
Boral, Debasish;Liu, Haowen N.;Marchetti, Dario
通讯作者：
Marchetti, Dario
DOI：
10.6004/jnccn.2016.0003
发表时间：
2016-01-01
影响因子：
13.4
作者：
Blau, C. Anthony;Ramirez, Arturo B.;Zhu, Jingchun
通讯作者：
Zhu, Jingchun