Gene expression profiles of inflammatory breast cancer reveal high heterogeneity across the epithelial-hybrid-mesenchymal spectrum

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dc.citation.articleNumber101026
dc.citation.issueNumber4
dc.citation.journalTitleTranslational Oncology
dc.citation.volumeNumber14
dc.contributor.authorChakraborty, Priyanka
dc.contributor.authorGeorge, Jason T
dc.contributor.authorWoodward, Wendy A
dc.contributor.authorLevine, Herbert
dc.contributor.authorJolly, Mohit Kumar
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2021-02-24T19:15:39Z
dc.date.available2021-02-24T19:15:39Z
dc.date.issued2021
dc.description.abstractInflammatory breast cancer (IBC) is a highly aggressive breast cancer that metastasizes largely via tumor emboli, and has a 5-year survival rate of less than 30%. No unique genomic signature has yet been identified for IBC nor has any specific molecular therapeutic been developed to manage the disease. Thus, identifying gene expression signatures specific to IBC remains crucial. Here, we compare various gene lists that have been proposed as molecular footprints of IBC using different clinical samples as training and validation sets and using independent training algorithms, and determine their accuracy in identifying IBC samples in three independent datasets. We show that these gene lists have little to no mutual overlap, and have limited predictive accuracy in identifying IBC samples. Despite this inconsistency, single-sample gene set enrichment analysis (ssGSEA) of IBC samples correlate with their position on the epithelial-hybrid-mesenchymal spectrum. This positioning, together with ssGSEA scores, improves the accuracy of IBC identification across the three independent datasets. Finally, we observed that IBC samples robustly displayed a higher coefficient of variation in terms of EMT scores, as compared to non-IBC samples. Pending verification that this patient-to-patient variability extends to intratumor heterogeneity within a single patient, these results suggest that higher heterogeneity along the epithelial-hybrid-mesenchymal spectrum can be regarded to be a hallmark of IBC and a possibly useful biomarker.
dc.identifier.citationChakraborty, Priyanka, George, Jason T, Woodward, Wendy A, et al.. "Gene expression profiles of inflammatory breast cancer reveal high heterogeneity across the epithelial-hybrid-mesenchymal spectrum." <i>Translational Oncology,</i> 14, no. 4 (2021) Elsevier: https://doi.org/10.1016/j.tranon.2021.101026.
dc.identifier.digital1-s20-S1936523321000188-main
dc.identifier.doihttps://doi.org/10.1016/j.tranon.2021.101026
dc.identifier.urihttps://hdl.handle.net/1911/110076
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an open access article under the CC BY-NC-ND license
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleGene expression profiles of inflammatory breast cancer reveal high heterogeneity across the epithelial-hybrid-mesenchymal spectrum
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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