期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-09018-y
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资金
- NBIS
- BioMS
- SciLifeLab proteogenomics core facilities
- Swedish Research Council
- Swedish Cancer Society
- Swedish Foundation for Strategic Research
- Stockholm County Council (ALF)
- Cancer Society in Stockholm
- AstraZeneca Smart Trial grant
- NCI [CA016672, U24CA209851, U24CA210949, U24CA210950]
- Komen [SAC110052]
- Breast Cancer Research Foundation [BCRF-16-109]
- Wenner-Gren Foundation
- Knut and Alice Wallenberg Foundation
- Norwegian Regional Health Authorities [2014061]
- National Microscopy Infrastructure, NMI [VR-RFI 2016-00968]
In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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