Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance

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.