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Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer
Advanced tumours are often heterogeneous, consisting of subclones with various genetic alterations and functional roles. The precise molecular features that characterize the contributions of multiscale intratumour heterogeneity to malignant progression, metastasis, and poor survival are largely unkn...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519071/ https://www.ncbi.nlm.nih.gov/pubmed/32978398 http://dx.doi.org/10.1038/s41467-020-18703-2 |
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author | Fan, Ming Xia, Pingping Clarke, Robert Wang, Yue Li, Lihua |
author_facet | Fan, Ming Xia, Pingping Clarke, Robert Wang, Yue Li, Lihua |
author_sort | Fan, Ming |
collection | PubMed |
description | Advanced tumours are often heterogeneous, consisting of subclones with various genetic alterations and functional roles. The precise molecular features that characterize the contributions of multiscale intratumour heterogeneity to malignant progression, metastasis, and poor survival are largely unknown. Here, we address these challenges in breast cancer by defining the landscape of heterogeneous tumour subclones and their biological functions using radiogenomic signatures. Molecular heterogeneity is identified by a fully unsupervised deconvolution of gene expression data. Relative prevalence of two subclones associated with cell cycle and primary immunodeficiency pathways identifies patients with significantly different survival outcomes. Radiogenomic signatures of imaging scale heterogeneity are extracted and used to classify patients into groups with distinct subclone compositions. Prognostic value is confirmed by survival analysis accounting for clinical variables. These findings provide insight into how a radiogenomic analysis can identify the biological activities of specific subclones that predict prognosis in a noninvasive and clinically relevant manner. |
format | Online Article Text |
id | pubmed-7519071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75190712020-10-14 Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer Fan, Ming Xia, Pingping Clarke, Robert Wang, Yue Li, Lihua Nat Commun Article Advanced tumours are often heterogeneous, consisting of subclones with various genetic alterations and functional roles. The precise molecular features that characterize the contributions of multiscale intratumour heterogeneity to malignant progression, metastasis, and poor survival are largely unknown. Here, we address these challenges in breast cancer by defining the landscape of heterogeneous tumour subclones and their biological functions using radiogenomic signatures. Molecular heterogeneity is identified by a fully unsupervised deconvolution of gene expression data. Relative prevalence of two subclones associated with cell cycle and primary immunodeficiency pathways identifies patients with significantly different survival outcomes. Radiogenomic signatures of imaging scale heterogeneity are extracted and used to classify patients into groups with distinct subclone compositions. Prognostic value is confirmed by survival analysis accounting for clinical variables. These findings provide insight into how a radiogenomic analysis can identify the biological activities of specific subclones that predict prognosis in a noninvasive and clinically relevant manner. Nature Publishing Group UK 2020-09-25 /pmc/articles/PMC7519071/ /pubmed/32978398 http://dx.doi.org/10.1038/s41467-020-18703-2 Text en © The Author(s) 2020 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/. |
spellingShingle | Article Fan, Ming Xia, Pingping Clarke, Robert Wang, Yue Li, Lihua Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer |
title | Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer |
title_full | Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer |
title_fullStr | Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer |
title_full_unstemmed | Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer |
title_short | Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer |
title_sort | radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519071/ https://www.ncbi.nlm.nih.gov/pubmed/32978398 http://dx.doi.org/10.1038/s41467-020-18703-2 |
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