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Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance

De Marchi, Tommaso LU ; Pyl, Paul Theodor LU ; Sjöström, Martin LU ; Klasson, Stina LU ; Sartor, Hanna LU ; Tran, Lena LU ; Pekar, Gyula ; Malmström, Johan LU orcid ; Malmström, Lars LU and Niméus, Emma LU (2021) In Journal of Proteome Research 20(5). p.2983-3001
Abstract

Proteogenomic approaches have enabled the generat̲ion of novel information levels when compared to single omics studies although burdened by extensive experimental efforts. Here, we improved a data-independent acquisition mass spectrometry proteogenomic workflow to reveal distinct molecular features related to mammographic appearances in breast cancer. Our results reveal splicing processes detectable at the protein level and highlight quantitation and pathway complementarity between RNA and protein data. Furthermore, we confirm previously detected enrichments of molecular pathways associated with estrogen receptor-dependent activity and provide novel evidence of epithelial-to-mesenchymal activity in mammography-detected spiculated... (More)

Proteogenomic approaches have enabled the generat̲ion of novel information levels when compared to single omics studies although burdened by extensive experimental efforts. Here, we improved a data-independent acquisition mass spectrometry proteogenomic workflow to reveal distinct molecular features related to mammographic appearances in breast cancer. Our results reveal splicing processes detectable at the protein level and highlight quantitation and pathway complementarity between RNA and protein data. Furthermore, we confirm previously detected enrichments of molecular pathways associated with estrogen receptor-dependent activity and provide novel evidence of epithelial-to-mesenchymal activity in mammography-detected spiculated tumors. Several transcript-protein pairs displayed radically different abundances depending on the overall clinical properties of the tumor. These results demonstrate that there are differentially regulated protein networks in clinically relevant tumor subgroups, which in turn alter both cancer biology and the abundance of biomarker candidates and drug targets.

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Please use this url to cite or link to this publication:
@article{d00ee1d6-522e-46b2-ab6e-2b0ff2ac19d4,
  abstract     = {{<p>Proteogenomic approaches have enabled the generat̲ion of novel information levels when compared to single omics studies although burdened by extensive experimental efforts. Here, we improved a data-independent acquisition mass spectrometry proteogenomic workflow to reveal distinct molecular features related to mammographic appearances in breast cancer. Our results reveal splicing processes detectable at the protein level and highlight quantitation and pathway complementarity between RNA and protein data. Furthermore, we confirm previously detected enrichments of molecular pathways associated with estrogen receptor-dependent activity and provide novel evidence of epithelial-to-mesenchymal activity in mammography-detected spiculated tumors. Several transcript-protein pairs displayed radically different abundances depending on the overall clinical properties of the tumor. These results demonstrate that there are differentially regulated protein networks in clinically relevant tumor subgroups, which in turn alter both cancer biology and the abundance of biomarker candidates and drug targets.</p>}},
  author       = {{De Marchi, Tommaso and Pyl, Paul Theodor and Sjöström, Martin and Klasson, Stina and Sartor, Hanna and Tran, Lena and Pekar, Gyula and Malmström, Johan and Malmström, Lars and Niméus, Emma}},
  issn         = {{1535-3893}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{5}},
  pages        = {{2983--3001}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Proteome Research}},
  title        = {{Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance}},
  url          = {{http://dx.doi.org/10.1021/acs.jproteome.1c00243}},
  doi          = {{10.1021/acs.jproteome.1c00243}},
  volume       = {{20}},
  year         = {{2021}},
}