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

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dc.contributor.authorFan, Mingen
dc.contributor.authorXia, Pingpingen
dc.contributor.authorClarke, Roberten
dc.contributor.authorWang, Yueen
dc.contributor.authorLi, Lihuaen
dc.contributor.departmentElectrical and Computer Engineeringen
dc.date.accessioned2021-02-04T19:45:06Zen
dc.date.available2021-02-04T19:45:06Zen
dc.date.issued2020-09-25en
dc.description.abstractAdvanced 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. Tumours are made up of heterogeneous subclones. Here, the authors show using breast cancer imaging and gene expression datasets that these subclones can be inferred by the deconvolution of gene expression data, mapped to MRI derived radiogenomic signatures and used to estimate prognosis.en
dc.description.notesThis 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).en
dc.description.sponsorshipNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [61731008, 61871428]; Natural Science Foundation of Zhejiang Province of ChinaNatural Science Foundation of Zhejiang Province [LJ19H180001]; US National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA184902, HL111362-05A1]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41467-020-18703-2en
dc.identifier.issn2041-1723en
dc.identifier.issue1en
dc.identifier.other4861en
dc.identifier.pmid32978398en
dc.identifier.urihttp://hdl.handle.net/10919/102232en
dc.identifier.volume11en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleRadiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast canceren
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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