title: System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis.
abstract: The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Pozniak
authors.affiliation: Institute of Pathology, Sheba Medical Center, Tel Hashomer 5265601, Israel.
authors.forename: Nora
authors.initials: N
authors.lastname: Balint-Lahat
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; School of Computer Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Jan Daniel
authors.initials: JD
authors.lastname: Rudolph
authors.affiliation: Department of Immunology Genetics and Pathology, Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindskog
authors.affiliation: Department of Computer Science & Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Rotem
authors.initials: R
authors.lastname: Katzir
authors.affiliation: Institute of Pathology, Sheba Medical Center, Tel Hashomer 5265601, Israel.
authors.forename: Camilla
authors.initials: C
authors.lastname: Avivi
authors.affiliation: Department of Immunology Genetics and Pathology, Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.affiliation: School of Computer Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; Department of Computer Science & Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA; Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Eytan
authors.initials: E
authors.lastname: Ruppin
authors.affiliation: Institute of Pathology, Sheba Medical Center, Tel Hashomer 5265601, Israel; Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: geiger@tauex.tau.ac.il.
authors.forename: Tamar
authors.initials: T
authors.lastname: Geiger
mesh_terms: D001943:Breast Neoplasms; D006706:Homeostasis; D006801:Humans; D008207:Lymphatic Metastasis; D013058:Mass Spectrometry; D040901:Proteomics