期刊
CONVERGENT SCIENCE PHYSICAL ONCOLOGY
卷 4, 期 1, 页码 -出版社
IOP PUBLISHING LTD
DOI: 10.1088/2057-1739/aaa00b
关键词
prostate cancer; tumor heterogeneity; metastatic tumor cells; liquid biopsies; circulating tumor cells; high definition single cell analysis (HD-SCA)
类别
资金
- Prostate Cancer Foundation Challenge Award [17CHAL04]
- Prostate Cancer Foundation-Movember Foundation USA Award [17CHAL01]
- Prostate Cancer Foundation-Movember Foundation [16CHAL04]
- DOD CDMRP [PC130244]
- Federal funds from the National Cancer Institute [PO1CA098912]
- National Cancer Institute, National Institutes of Health, Leidos Biomedical Research [HHSN261200800001E]
- Jean Perkins Foundation
- David and Janet Polak Foundation Fellowship in Convergent Science
- Schlegel Family Endowed Fellowship Fund
- Kalayil and Leela Chacko, MD Fellowship
- CDMRP [PC130244, 672384] Funding Source: Federal RePORTER
Tumor heterogeneity is prevalent in both treatment-naive and end-stage metastatic castration-resistant prostate cancer (PCa), and may contribute to the broad range of clinical presentation, treatment response, and disease progression. To characterize molecular heterogeneity associated with de novo metastatic PCa, multiplatform single cell profiling was performed using high definition single cell analysis (HD-SCA). HD-SCA enabled morphoproteomic and morphogenomic profiling of single cells from touch preparations of tissue cores (prostate and bone marrow biopsies) as well as liquid samples (peripheral blood and bone marrow aspirate). Morphology, nuclear features, copy number alterations, and protein expression were analyzed. Tumor cells isolated from prostate tissue touch preparation (PTTP) and bone marrow touch preparation (BMTP) as well as metastatic tumor cells (MTCs) isolated from bone marrow aspirate were characterized by morphology and cytokeratin expression. Although peripheral blood was examined, circulating tumor cells were not definitively observed. Targeted proteomics of PTTP, BMTP, and MTCs revealed cell lineage and luminal prostate epithelial differentiation associated with PCa, including co-expression of EpCAM, PSA, and PSMA. Androgen receptor expression was highest in MTCs. Hallmark PCa copy number alterations, including PTEN and ETV6 deletions and NCOA2 amplification, were observed in cells within the primary tumor and bone marrow biopsy samples. Genomic landscape of MTCs revealed to be a mix of both primary and bone metastatic tissue. This multiplatform analysis of single cells reveals several clonal origins of metastatic PCa in a newly diagnosed, untreated patient with polymetastatic disease. This case demonstrates that real-time molecular profiling of cells collected through prostate and bone marrow biopsies is feasible and has the potential to elucidate the origin and evolution of metastatic tumor cells. Altogether, biological and genomic data obtained through longitudinal biopsies can be used to reveal the properties of PCa and can impact clinical management.
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