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

Ming Fan, Pingping Xia, Robert R Clarke, Yue Wang, Lihua Li

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Article number4861
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (61731008, 61871428), the Natural Science Foundation of Zhejiang Province of China (LJ19H180001), and the US National Institutes of Health (CA184902 and HL111362-05A1).

Publisher Copyright:
© 2020, The Author(s).

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural

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