Proteomic analysis of serum yields six candidate proteins that are differentially regulated in a subset of women with endometriosis

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Fertility and sterility (Impact Factor: 4.59). 03/2009; 93(7):2137-44. DOI: 10.1016/j.fertnstert.2008.12.121
Source: PubMed


To identify potential novel biomarkers that differ between subjects with and without endometriosis and that might aid in developing a noninvasive, serum-based diagnostic test.
Case-control evaluation of a diagnostic test.
University medical center.
Consenting women of reproductive age undergoing laparoscopy for indications of pain, infertility, elective tubal ligation, tubal reanastomosis, or other benign indication.
Diagnostic laparoscopy and peripheral venipuncture.
Concentrations of low-molecular-weight proteins in serum; surgical staging of endometriosis.
Six proteins were found that were differentially expressed between those with and without disease and that had good diagnostic properties. Taken together in a two-step diagnostic algorithm, we were able to diagnose 55% of subjects, with 99% accuracy as to the status of disease. Further combining this algorithm with that derived by our previous study of serum putative markers (monocyte chemoattractant protein-1, migration inhibitory factor, leptin, and CA-125) improved our diagnostic capability to 73% of subjects, with 94% overall accuracy.
This study is the critical first step in the identification of potential novel biomarkers of endometriosis. Future identification of the proteins and further validation in a second population is needed before applying these findings in clinical practice.

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    • "The manifested symptoms of endometriosis are most commonly pelvic pain and infertility as the lesions develop and establish within the peritoneal region. Although there is a delay in the diagnosis of endometriosis, it has been noted that the most common symptoms are dysmenorrhea, pelvic pain, dyspareunia, and infertility [48]. A diagnosis of endometriosis is established in 17% of women who present with primary infertility, 5–21% of women with pelvic pain, and 50% of adolescents with dysmenorrhea [64]. "
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    ABSTRACT: PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions.
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    • "Also, nerve samples from patients with complex regional pain syndrome (CRPS) have been analyzed in order to detect up/down regulated proteins [17]. Proteomics of serum have been used for the identification of possible biomarkers of chronic endometriosis [18], [19]. In addition, several proteomic studies have investigated human skeletal muscle exposed to high altitude [20], bed rest [21], [22], and exercise [23]. "
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    • "Proteins that are involved in pain are important to investigate due to the fact that they can act as signal substances, activate the formation of algesics and control nociceptive processes. The number of studies investigating the human proteome in body fluids and tissues in human chronic pain conditions are limited e.g., [17]–[22], [35]–[37]. There are also a few examples of proteomic studies in acute pain e.g., acute coronary syndrome [38], after eccentric exercises [39] and experimental cutaneous injury [40]. "
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