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Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case
Little is known about the complexity and plasticity of circulating tumor cell (CTC) biology in different compartments of the fluid microenvironment during tumor metastasis. Here we integrated phenomics, genomics, and targeted proteomics to characterize CTC phenotypic and genotypic heterogeneity in p...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213535/ https://www.ncbi.nlm.nih.gov/pubmed/35729213 http://dx.doi.org/10.1038/s41698-022-00289-1 |
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author | Chai, Shoujie Ruiz-Velasco, Carmen Naghdloo, Amin Pore, Milind Singh, Mohan Matsumoto, Nicholas Kolatkar, Anand Xu, Liya Shishido, Stephanie Aparicio, Ana Zurita, Amado J. Hicks, James Kuhn, Peter |
author_facet | Chai, Shoujie Ruiz-Velasco, Carmen Naghdloo, Amin Pore, Milind Singh, Mohan Matsumoto, Nicholas Kolatkar, Anand Xu, Liya Shishido, Stephanie Aparicio, Ana Zurita, Amado J. Hicks, James Kuhn, Peter |
author_sort | Chai, Shoujie |
collection | PubMed |
description | Little is known about the complexity and plasticity of circulating tumor cell (CTC) biology in different compartments of the fluid microenvironment during tumor metastasis. Here we integrated phenomics, genomics, and targeted proteomics to characterize CTC phenotypic and genotypic heterogeneity in paired peripheral blood (PB) and bone marrow aspirate (BMA) from a metastatic prostate cancer patient following the rapid disease progression, using the High-Definition Single Cell Assay 3.0 (HDSCA3.0). Uniquely, we identified a subgroup of genetically clonal CTCs that acquired a mesenchymal-like state and its presence was significantly associated with one subclone that emerged along the clonal lineage. Higher CTC abundance and phenotypic diversity were observed in the BMA than PB and differences in genomic alterations were also identified between the two compartments demonstrating spatial heterogeneity. Single cell copy number profiling further detected clonal heterogeneity within clusters of CTCs (also known as microemboli or aggregates) as well as phenotypic variations by targeted proteomics. Overall, these results identify epithelial and mesenchymal CTCs in the clonal lineage of an aggressive prostate cancer case and also demonstrate a single cell multi-omic approach to deconvolute the heterogeneity and association of CTC phenotype and genotype in multi-medium liquid biopsies of metastatic prostate cancer. |
format | Online Article Text |
id | pubmed-9213535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92135352022-06-23 Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case Chai, Shoujie Ruiz-Velasco, Carmen Naghdloo, Amin Pore, Milind Singh, Mohan Matsumoto, Nicholas Kolatkar, Anand Xu, Liya Shishido, Stephanie Aparicio, Ana Zurita, Amado J. Hicks, James Kuhn, Peter NPJ Precis Oncol Case Report Little is known about the complexity and plasticity of circulating tumor cell (CTC) biology in different compartments of the fluid microenvironment during tumor metastasis. Here we integrated phenomics, genomics, and targeted proteomics to characterize CTC phenotypic and genotypic heterogeneity in paired peripheral blood (PB) and bone marrow aspirate (BMA) from a metastatic prostate cancer patient following the rapid disease progression, using the High-Definition Single Cell Assay 3.0 (HDSCA3.0). Uniquely, we identified a subgroup of genetically clonal CTCs that acquired a mesenchymal-like state and its presence was significantly associated with one subclone that emerged along the clonal lineage. Higher CTC abundance and phenotypic diversity were observed in the BMA than PB and differences in genomic alterations were also identified between the two compartments demonstrating spatial heterogeneity. Single cell copy number profiling further detected clonal heterogeneity within clusters of CTCs (also known as microemboli or aggregates) as well as phenotypic variations by targeted proteomics. Overall, these results identify epithelial and mesenchymal CTCs in the clonal lineage of an aggressive prostate cancer case and also demonstrate a single cell multi-omic approach to deconvolute the heterogeneity and association of CTC phenotype and genotype in multi-medium liquid biopsies of metastatic prostate cancer. Nature Publishing Group UK 2022-06-21 /pmc/articles/PMC9213535/ /pubmed/35729213 http://dx.doi.org/10.1038/s41698-022-00289-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Case Report Chai, Shoujie Ruiz-Velasco, Carmen Naghdloo, Amin Pore, Milind Singh, Mohan Matsumoto, Nicholas Kolatkar, Anand Xu, Liya Shishido, Stephanie Aparicio, Ana Zurita, Amado J. Hicks, James Kuhn, Peter Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case |
title | Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case |
title_full | Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case |
title_fullStr | Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case |
title_full_unstemmed | Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case |
title_short | Identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case |
title_sort | identification of epithelial and mesenchymal circulating tumor cells in clonal lineage of an aggressive prostate cancer case |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213535/ https://www.ncbi.nlm.nih.gov/pubmed/35729213 http://dx.doi.org/10.1038/s41698-022-00289-1 |
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