Endometriosis Comparative Proteomics And Related Protein Identification And Expression

BackgroundEndometriosis is a common gynecological disorder, affecting 15～20% women in theirreproductive age. It frequently associates with pelvic pain and infertility. Endometriosis is observed in multiple sites with various and complicated lesions, and it is characterized with strong invasive ability and frequent recurrence. The pathogenesis of endometriosis is poorly understood. Its diagnosis and treatment present a great challenge to the gynecologists. Accurate and non-invasive diagnostic techniques are urgently needed if the clinical management of endometriosis is to be more effective. Proteomic technologies, as the frontier of life science, provide sensitive, fast and high throughput tools for the research of endometriosis. Using proteomic technologies we can separate and identify differently expressed proteins in endometriums and sera of patients with endometriosis. These proteins may play an important role in the pathogenesis of endometriosis and be related to the degree and state of endometriosis. Thus, proteomic technologies provide strong methods to discover new biomarkers of endometriosis and targets for its diagnosis and treatment.ObjectiveTo investigate the differently expressed proteins in endometriosis and adenomyosis identified by two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass Spectrometry (MALDI-TOF-MS) in former experiments; To set up serum protein expression profiling of patients with endometriosis, and identify the endometriosis-specific proteins; to investigate the pathogenesis of endometriosis and find biomarkers for the diagnosis of endometriosis.Methods1. The expression of stathmin and Annexin-1 in eutopic endometrium of women with and without endometriosis was detected by Real-Time PCR, immunohistochemistry and Western blot.2. The differently expressed proteins were identified by 2DE and MALDI-TOF-MS, and some specific protein was further investigated by Western Blot and immunohistochemistry. 3. The differently expressed proteins in serum of patients with endometriosis were analyzed by SELDI-TOF-MS technique.Results1. The expression of stathmin and Annexin-l was increased in eutopic endometrium of patients with endometriosis.2. Set up a stable serum protein expression profile of women with or without endometriosis. Twelve differently expressed proteins were identified, which are involved in cell skeleton, cellular activity and metabolism.3. Western Blot showed that the serum level of CK1 was increased in patients with endometriosis.4. Stable serum fingerprints of endometriosis were set up and twenty-six differently expressed proteins were identified.5,The diagnostic model composed of the peak M/Z 5632 Da and M/Z 8235 Da has ideal sensitivity and specificity for the diagnosis of endometriosis. The peak M/Z 5632 Da has high sensitivity and specificity for the differential diagnosis of endometriosis with ovarian cancer.Conclusions1. Both Stathmin and Annexin-l play important role in the regulation of cell activities. In our study the expression of stathmin and Annexin-l increase in the eutopic endometrium of women with endometriosis and both may be involved in the pathogenesis of endometriosis. Our results further confirm the theory that the eutopic endometrium of women with endometriosis may be innately abnormal and play a central role in the pathogenesis of endometriosis.2. By 2DE and MALDI-TOF-MS, we identified twelve differently expressed proteins in the sera of women with endometriosis, which are involved in cell skeleton, cellular activity and metabolism. These proteins may play an important role in the pathogenesis of endometriosis and may be applied as serum biomarkers of endometriosis.3. Cytokeratins (CKs) is a family of cell skeletons. The level of CK1 in sera of patients with endometriosis is increased and it may be a potential biomarker for the diagnosis of endometriosis.4. We compared the differently expressed proteins in sera of women with endometriosis, benign or malignant ovarian tumors and healthy women, and established diagnosis models, which have high sensitivity and specificity for the diagnosis of endometriosis and its differential diagnosis with ovarian cancer. These results may be helpful to understand the pathogenesis of endometriosis and provide potential biomarkers for its diagnosis.