Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance.
Tommaso De MarchiPaul Theodor PylMartin SjöströmStina KlassonHanna SartorLena TranGyula PekarJohan MalmströmLars MalmströmEmma NiméusPublished in: Journal of proteome research (2021)
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.
Keyphrases
- mass spectrometry
- electronic health record
- estrogen receptor
- protein protein
- amino acid
- single cell
- squamous cell carcinoma
- emergency department
- healthcare
- gene expression
- small molecule
- ms ms
- machine learning
- dna methylation
- high performance liquid chromatography
- rna seq
- breast cancer risk
- big data
- papillary thyroid
- transcription factor
- data analysis