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

ABSTRACT 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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    • "Therefore, newly available technologies could play a key role in the identification of novel biological markers in the early stages of endometriosis. Recently, several investigators have advocated the use of proteomic technologies in endometriosis research and have demonstrated that several proteins are differently expressed in various body fluids, including serum, plasma, peritoneal and endometrial fluids and urine of patients with endometriosis versus those without this condition (Ametzazurra et al., 2009; Ferrero et al., 2007; Liu et al., 2007; Seeber et al., 2010; Tokushige et al., 2011). Proteomic approaches enable the comparison of protein expression in cells, tissues or body fluids under various conditions . "
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    ABSTRACT: Recently, proteomic technologies have demonstrated that several proteins are differently expressed in various body fluids of patients with endometriosis compared with those without this condition. The aim of this study was to investigate proteins secreted in urine of patients with endometriosis using proteomic techniques in order to identify potential markers for the clinical diagnosis of endometriosis. Urine samples were collected from women undergoing laparoscopy for different indications including pelvic masses, pelvic pain, suspicious endometriosis, infertility and diagnostic evaluation. Proteomic techniques and mass spectrometry were used to identify proteins secreted in the urine of the patients with and without endometriosis and quantification of identified protein was performed using western blot and specific commercial sandwich enzyme-linked immunosorbent assays (ELISA). Twenty-two protein spots were differentially expressed in the urine of patients with and without endometriosis, one of which was identified as urinary vitamin D-binding protein (VDBP). ELISA quantification of urinary VDBP corrected for creatinine expression (VDBP-Cr) revealed that urinary VDBP-Cr was significantly greater in patients with endometriosis than in those without (111.96 ± 74.59 versus 69.90 ± 43.76 ng/mg Cr, P = 0.001). VDBP-Cr had limited value as a diagnostic marker for endometriosis (Sensitivity 58%, Specificity 76%). When combined with serum CA-125 levels (the product of serum CA-125 and urinary VDBP-Cr), it did not significantly increase the diagnostic power of serum CA-125 alone. Urinary VDBP levels are elevated in patients with endometriosis. They have limited value as a potential diagnostic biomarker for endometriosis but suggest it would be worthwhile to investigate other urinary proteins for this purpose.
    Human Reproduction 12/2011; 27(2):515-22. DOI:10.1093/humrep/der345 · 4.59 Impact Factor
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    • "Mihalyi et al. (2010) reported six plasma biomarkers , interleukin-6 (IL-6), IL-8, tumour necrosis factor a (TNFa), high-sensitivity C-reactive protein (hSCRP), CA125 and CA19-9, for non-invasive diagnosis of endometriosis; however, they are not very specific to endometriosis. Proteomic technologies such as matrixassisted laser desorption/ionization-time-of-flight/mass spectrometry (MALDI-TOF/MS) and surface-enhanced laser desorption/ionization (SELDI)-TOF/MS have also been used to identify the biomarkers for diagnosis of endometriosis (Zhang et al., 2006a,b; Fowler et al., 2007; Ametzazurra et al., 2009; Seeber et al., 2010). However, the discovery of biomarkers with high sensitivity, specificity and clinical relevance useful for non-invasive diagnosis of endometriosis, is still awaited. "
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    ABSTRACT: Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis. A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation. The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis. Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.
    Human Reproduction 12/2011; 27(2):408-17. DOI:10.1093/humrep/der410 · 4.59 Impact Factor
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    ABSTRACT: A new adaptive blind source separation (BSS) algorithm is presented in this paper. The algorithm uses a special cost function mid only the second order statistical information of the colored signals to perform the pre-whitening transform and orthogonal transform, which avoids the singular value decomposition (SVD) as commonly used in off-line BSS operation and makes two-steps adaptive BSS operation possible. Simulations showed the good separation performance of the algorithm.
    Signal Processing, 2004. Proceedings. ICSP '04. 2004 7th International Conference on; 01/2004
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