title: Concordant release of glycolysis proteins into the plasma preceding a diagnosis of ER+ breast cancer.
abstract: Although the identification of peripheral blood biomarkers would enhance early detection strategies for breast cancer, the discovery of protein markers has been challenging. In this study, we sought to identify coordinated changes in plasma proteins associated with breast cancer based on large-scale quantitative mass spectrometry. We analyzed plasma samples collected up to 74 weeks before diagnosis from 420 estrogen receptor (ER)(+) cases and matched controls enrolled in the Women's Health Initiative cohort. A gene set enrichment analysis was applied to 467 quantified proteins, linking their corresponding genes to particular biologic pathways. On the basis of differences in the concentration of individual proteins, glycolysis pathway proteins exhibited a statistically significant difference between cases and controls. In particular, the enrichment was observed among cases in which blood was drawn closer to diagnosis (effect size for the 0-38 weeks prediagnostic group, 1.91; P, 8.3E-05). Analysis of plasmas collected at the time of diagnosis from an independent set of cases and controls confirmed upregulated levels of glycolysis proteins among cases relative to controls. Together, our findings indicate that the concomitant release of glycolysis proteins into the plasma is a pathophysiologic event that precedes a diagnosis of ER(+) breast cancer.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, School of Medicine, University of Washington, Seattle, Washington 98109, USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Amon
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Pitteri
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Li
authors.forename: Martin
authors.initials: M
authors.lastname: McIntosh
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Ladd
authors.forename: Mary
authors.initials: M
authors.lastname: Disis
authors.forename: Peggy
authors.initials: P
authors.lastname: Porter
authors.forename: Chee Hong
authors.initials: CH
authors.lastname: Wong
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Paul
authors.initials: P
authors.lastname: Lampe
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.forename: Samir M
authors.initials: SM
authors.lastname: Hanash
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D011960:Receptors, Estrogen / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen