Application of serum proteomics to the Women's Health Initiative conjugated equine estrogens trial reveals a multitude of effects relevant to clinical findings

Hiroyuki Katayama, Sophie Paczesny, Ross Prentice, Aaron Aragaki, Vitor M. Faca, Sharon J. Pitteri, Qing Zhang, Hong Wang, Melissa Silva, Jacob Kennedy, Jacques Rossouw, Rebecca Jackson, Judith Hsia, Rowan Chlebowski, Jo Ann Manson, Samir Hanash

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31 Scopus citations

Abstract

Background: The availability of serum collections from the Women's Health Initiative (WHI) conjugated equine estrogens (CEE) randomized controlled trial provides an opportunity to test the potential of in-depth quantitative proteomics to uncover changes in the serum proteome related to CEE and to assess their relevance to trial findings, including elevations in the risk of stroke and venous thromboembolism and a reduction in fractures. Methods: Five independent large scale quantitative proteomics analyses were performed, each comparing a set of pooled serum samples collected from 10 subjects, 1 year following initiation of CEE at 0.625 mg/d, relative to their baseline pool. A subset of proteins that exhibited increased levels with CEE by quantitative proteomics was selected for validation studies. Results: Of 611 proteins quantified based on differential stable isotope labeling, the levels of 116 (19%) were changed after 1 year of CEE (nominal P < 0.05), while 64 of these had estimated false discovery rates <0.05. Most of the changed proteins were not previously known to be affected by CEE and had relevance to processes that included coagulation, metabolism, osteogenesis, inflammation, and blood pressure maintenance. To validate quantitative proteomic data, 14 proteins were selected for ELISA. Findings for ten - IGF1, IGFBP4, IGFBP1, IGFBP2, F10, AHSG, GC, CP, MMP2, and PROZ - were confirmed in the initial set of 50 subjects and further validated in an independent set of 50 additional subjects who received CEE.

Original languageEnglish (US)
Article numbergm47
JournalGenome Medicine
Volume1
Issue number4
DOIs
StatePublished - Apr 29 2009

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Katayama, H., Paczesny, S., Prentice, R., Aragaki, A., Faca, V. M., Pitteri, S. J., Zhang, Q., Wang, H., Silva, M., Kennedy, J., Rossouw, J., Jackson, R., Hsia, J., Chlebowski, R., Manson, J. A., & Hanash, S. (2009). Application of serum proteomics to the Women's Health Initiative conjugated equine estrogens trial reveals a multitude of effects relevant to clinical findings. Genome Medicine, 1(4), [gm47]. https://doi.org/10.1186/gm47