title: Ovarian endometriosis signatures established through discovery and directed mass spectrometry analysis.
abstract: New molecular information on potential therapeutic targets or tools for noninvasive diagnosis for endometriosis are important for patient care and treatment. However, surprisingly few efforts have described endometriosis at the protein level. In this work we enumerate the proteins in patient endometrium and ovarian endometrioma by extensive and comprehensive analysis of minute amounts of cryosectioned tissues in a three-tiered mass spectrometric approach. Quantitative comparison of the tissues revealed 214 differentially expressed proteins in ovarian endometrioma and endometrium. These proteins are reported here as a resource of SRM (selected reaction monitoring) assays that are unique, standardized, and openly available. Pathway analysis of the proteome measurements revealed a potential role for Transforming growth factor β-1 in ovarian endometriosis development. Subsequent mRNA microarray analysis further revealed clear ovarian endometrioma specificity for a subset of these proteins, which was also supported by further in silico studies. In this process two important proteins emerged, Calponin-1 and EMILIN-1, that were additionally confirmed in ovarian endometrioma tissues by immunohistochemistry and Western blotting. This study provides the most comprehensive molecular description of ovarian endometriosis to date and researchers with new molecular methods and tools for high throughput patient screening using the SRM assays.
authors.affiliation: Turku Centre for Biotechnology, ‡Department of Physiology, Institute of Biomedicine, ⊥Department of Mathematics and Statistics, and ¶Turku Center for Disease Modeling, University of Turku , Turku, Finland.
authors.forename: Anni P
authors.initials: AP
authors.lastname: Vehmas
authors.forename: Dorota
authors.initials: D
authors.lastname: Muth-Pawlak
authors.forename: Kaisa
authors.initials: K
authors.lastname: Huhtinen
authors.forename: Taija
authors.initials: T
authors.lastname: Saloniemi-Heinonen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Jaakkola
authors.forename: Teemu D
authors.initials: TD
authors.lastname: Laajala
authors.forename: Heidi
authors.initials: H
authors.lastname: Kaprio
authors.forename: Pia A
authors.initials: PA
authors.lastname: Suvitie
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
authors.forename: Harri
authors.initials: H
authors.lastname: Siitari
authors.forename: Antti
authors.initials: A
authors.lastname: Perheentupa
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.forename: Garry L
authors.initials: GL
authors.lastname: Corthals
mesh_terms: D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010049:Ovarian Diseases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D011506:Proteins; D053773:Transforming Growth Factor beta1; D000096985:Calponins; C030340:elastin microfibril interface located protein
keywords: AIMS; SRM; Western blot; endometriosis; immunohistochemistry; mass spectrometry; proteotypic peptides; quantitative proteomics; selected reaction monitoring; tissue