An Image-Based Identification of Aggressive Breast Cancer Circulating Tumor Cell Subtypes

被引:2
作者
Kamal, Mohamed [1 ,2 ,3 ,6 ]
Wang, Yiru Jess [1 ,2 ,4 ]
Plummer, Sarai [1 ,2 ]
Dickerson, Amber [1 ,2 ]
Yu, Min [1 ,2 ,4 ,5 ]
机构
[1] Univ Southern Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90033 USA
[2] Univ Southern Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA
[3] Univ Benha, Fac Sci, Dept Zool, Banha 13518, Egypt
[4] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA
[5] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum NCI Comprehens Canc C, Baltimore, MD 21201 USA
[6] Univ Southern Calif, Michelson Ctr Convergent Biosci, Dornsife Coll Letters Arts & Sci, Convergent Sci Inst Canc, 1002 Childs Way MCB 220, Los Angeles, CA 90089 USA
关键词
breast cancer; circulating tumor cells; heterogeneity; morphometric analyses; prognosis; PROGRESSION-FREE; RNA-SEQ; METASTASIS; CHEMOTHERAPY; MORPHOLOGY; CARCINOMA; SURVIVAL; MARKERS; RESISTANCE; PATIENT;
D O I
10.3390/cancers15102669
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Using previously established CTC lines from breast cancer patients, we identified different morphometric subgroups of CTCs with one of them having the highest tumorigenic potential in vivo despite the slowest cell proliferation in vitro. This subgroup represents 32% of all cells and contains cells with small cell volume, large nucleus to cell, dense nuclear areas to the nucleus, mitochondria to cell volume ratios and rough texture of cell membrane and termed "Small cell, Large mitochondria, Rough membrane" (SLR). RNA-seq analyses showed that the SLR group is enriched in pathways and cellular processes related to DNA replication, DNA repair and metabolism. SLR upregulated genes are associated with poor survival in patients with ER+ breast cancer based on the KM Plotter database. The high tumorigenic potential, slow proliferation, and enriched DNA replication/repair pathways suggest that the SLR subtype is associated with stemness properties. Our new findings provide a simple image-based identification of CTC subpopulations with elevated aggressiveness, which is expected to provide a more accurate prediction of patient survival and therapy response than total CTC numbers. The detection of morphometric and transcriptomic profiles related to the SLR subgroup of CTCs also opens opportunities for potential targeted cancer treatment.
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页数:18
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