Ovarian Endometriosis Signatures\nEstablished through\nDiscovery and Directed Mass Spectrometry Analysis

New\nmolecular information on potential therapeutic targets or tools\nfor noninvasive diagnosis for endometriosis are important for patient\ncare and treatment. However, surprisingly few efforts have described\nendometriosis at the protein level. In this work we enumerate the\nproteins in patient endometrium and ovarian endometrioma by extensive\nand comprehensive analysis of minute amounts of cryosectioned tissues\nin a three-tiered mass spectrometric approach. Quantitative comparison\nof the tissues revealed 214 differentially expressed proteins in ovarian\nendometrioma and endometrium. These proteins are reported here as\na resource of SRM (selected reaction monitoring) assays that are unique,\nstandardized, and openly available. Pathway analysis of the proteome\nmeasurements revealed a potential role for Transforming growth factor\nβ-1 in ovarian endometriosis development. Subsequent mRNA microarray\nanalysis further revealed clear ovarian endometrioma specificity for\na subset of these proteins, which was also supported by further in silico studies. In this process two important proteins\nemerged, Calponin-1 and EMILIN-1, that were additionally confirmed\nin ovarian endometrioma tissues by immunohistochemistry and Western\nblotting. This study provides the most comprehensive molecular description\nof ovarian endometriosis to date and researchers with new molecular\nmethods and tools for high throughput patient screening using the\nSRM assays.