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Gene expression predicts dormant metastatic breast cancer cell phenotype
BACKGROUND: Breast cancer can recur months to decades after an initial diagnosis and treatment. The mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and thus benefit from more rigorous screening and treatments. Unfortunate...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8800302/ https://www.ncbi.nlm.nih.gov/pubmed/35093137 http://dx.doi.org/10.1186/s13058-022-01503-5 |
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author | Ren, Qihao Khoo, Weng Hua Corr, Alexander P. Phan, Tri Giang Croucher, Peter I. Stewart, Sheila A. |
author_facet | Ren, Qihao Khoo, Weng Hua Corr, Alexander P. Phan, Tri Giang Croucher, Peter I. Stewart, Sheila A. |
author_sort | Ren, Qihao |
collection | PubMed |
description | BACKGROUND: Breast cancer can recur months to decades after an initial diagnosis and treatment. The mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and thus benefit from more rigorous screening and treatments. Unfortunately, the extreme rarity of dormant DTCs has been a major obstacle to their study. METHODS: To overcome this challenge, we developed an efficient system to isolate and study rare dormant breast cancer cells from metastatic organs including bones, which represent a major site of metastasis. After isolation of cells from the long bones, we used single cell RNA-sequencing (scRNA-seq) to profile proliferative and dormant PyMT-Bo1 breast cancer cells. We also compared this signature to dormant versus proliferative tumor cells isolated from the lungs. Finally, we compared our dormant signature to human datasets. RESULTS: We identified a group of genes including Cfh, Gas6, Mme and Ogn that were highly expressed in dormant breast cancer cells present in the bone and lung. Expression of these genes had no impact on dormancy in murine models, but their expression correlated with disease-free survival in primary human breast cancer tumors, suggesting that these genes have predictive value in determining which patients are likely to recur. CONCLUSIONS: Dormant breast cancer cells exhibit a distinct gene expression signature regardless of metastatic site. Genes enriched in dormant breast cancer cells correlate with recurrence-free survival in breast cancer patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01503-5. |
format | Online Article Text |
id | pubmed-8800302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88003022022-02-02 Gene expression predicts dormant metastatic breast cancer cell phenotype Ren, Qihao Khoo, Weng Hua Corr, Alexander P. Phan, Tri Giang Croucher, Peter I. Stewart, Sheila A. Breast Cancer Res Research Article BACKGROUND: Breast cancer can recur months to decades after an initial diagnosis and treatment. The mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and thus benefit from more rigorous screening and treatments. Unfortunately, the extreme rarity of dormant DTCs has been a major obstacle to their study. METHODS: To overcome this challenge, we developed an efficient system to isolate and study rare dormant breast cancer cells from metastatic organs including bones, which represent a major site of metastasis. After isolation of cells from the long bones, we used single cell RNA-sequencing (scRNA-seq) to profile proliferative and dormant PyMT-Bo1 breast cancer cells. We also compared this signature to dormant versus proliferative tumor cells isolated from the lungs. Finally, we compared our dormant signature to human datasets. RESULTS: We identified a group of genes including Cfh, Gas6, Mme and Ogn that were highly expressed in dormant breast cancer cells present in the bone and lung. Expression of these genes had no impact on dormancy in murine models, but their expression correlated with disease-free survival in primary human breast cancer tumors, suggesting that these genes have predictive value in determining which patients are likely to recur. CONCLUSIONS: Dormant breast cancer cells exhibit a distinct gene expression signature regardless of metastatic site. Genes enriched in dormant breast cancer cells correlate with recurrence-free survival in breast cancer patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01503-5. BioMed Central 2022-01-29 2022 /pmc/articles/PMC8800302/ /pubmed/35093137 http://dx.doi.org/10.1186/s13058-022-01503-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Ren, Qihao Khoo, Weng Hua Corr, Alexander P. Phan, Tri Giang Croucher, Peter I. Stewart, Sheila A. Gene expression predicts dormant metastatic breast cancer cell phenotype |
title | Gene expression predicts dormant metastatic breast cancer cell phenotype |
title_full | Gene expression predicts dormant metastatic breast cancer cell phenotype |
title_fullStr | Gene expression predicts dormant metastatic breast cancer cell phenotype |
title_full_unstemmed | Gene expression predicts dormant metastatic breast cancer cell phenotype |
title_short | Gene expression predicts dormant metastatic breast cancer cell phenotype |
title_sort | gene expression predicts dormant metastatic breast cancer cell phenotype |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8800302/ https://www.ncbi.nlm.nih.gov/pubmed/35093137 http://dx.doi.org/10.1186/s13058-022-01503-5 |
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