Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer

Ming Fan, Pingping Xia, Robert Clarke, Yue Wang () and Lihua Li ()
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Ming Fan: Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University
Pingping Xia: Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University
Robert Clarke: Hormel Institute, University of Minnesota
Yue Wang: Virginia Polytechnic Institute and State University
Lihua Li: Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-18703-2

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