Projects / Programmes
Biomarkers of endometriosis: proteomics and metabolomics approach
| Code |
Science |
Field |
Subfield |
| 3.05.00 |
Medical sciences |
Human reproduction |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
metabolomics, proteomics, biomarkers, diagnostic biomarkers, noninvasive diagnostics
Researchers (18)
Organisations (3)
Abstract
Endometriosis is a female reproductive disorder, characterized by the presence of endometrial tissue outside the uterine cavity. It affects an estimated 176 million women worldwide and is more frequent than cancer and diabetes. While the estimated prevalence is 6–10% in the general population, the frequency is 30%–50% in women with infertility and/or pain. The symptoms of endometriosis are non-specific. The golden standard for diagnosis is laparoscopy, a surgical visual inspection of the pelvic organs that requires an experienced surgeon, general anaesthesia and includes surgery associated risks. As a result of this, it can take up to 11 years before affected women are diagnosed and receive appropriate treatment. Although over 100 potential biomarkers of endometriosis were reported, neither a single one, nor a panel of biomarkers have been shown as clinically useful. Also other diagnostic methods such as transvaginal ultrasound, MRI and biomarker CA125 lack sufficient sensitivity and specificity, therefore endometriosis is usually discovered too late when complications including severe abdominal pain, inflammation and infertility are overt. A non-invasive test for reliable diagnosis of endometriosis is thus urgently needed. We hypothesize that biomarkers for noninvasive diagnostics of endometriosis can be identified with the proteomics and metabolomics approach. Our aims are: 1) to identify panels of blood proteins and metabolites specific for patients with endometriosis and 2) to develop diagnostic algorithms for clinical validation and application. We will collect blood samples (serum and plasma), clinical and epidemiological data and will employ targeted proteomics and metabolomics approaches followed by sound bioinformatics and multivariate statistics to develop diagnostic algorithms. Our case-control study will comprise 240 well defined patients with endometriosis like symptoms: 120 patients with laparoscopically and histologically proven endometriosis (ovarian, peritoneal and deep infiltrating) as a case group and a control group of 120 patients laparoscopicaly and histologically proven to be endometriosis free. Our targeted proteomics and metabolomics study will comprise discovery phase, where we aim to identify new proteins and metabolites associated with endometriosis on a smaller number of samples and the validation phase where we aim to determine concentrations of these proteins and metabolites on all case and control samples. Targeted proteomics will use antibody array technology (Panorama® Antibody Array) in the discovery phase to evaluate levels of 725 proteins and the high-throuput electrochemiluminiscence immunoassays (MSD® multiplex) in the validation phase. The targeted metabolomics will comprise ESI-MS/MS (Absolute IDQ p180) to evaluate 180 lipid metabolites in the discovery and the validation phase. The study will be performed in collaboration with Department of Gynecology, UMC Ljubljana, Center for Functional Genomics and Biochips at the Faculty of Medicine UL, Faculty of Biotechnology UL, and Helmholtz Zentrum Munchen. This will be the first study that will address combined targeted proteomics and metabolomics approach on endometriosis with the final aim to provide novel diagnostic algorithms.
Significance for science
The project J3-6799 focused mainly on lipids, important signalling molecules, which regulate different cellular processes related to endometriosis. This targeted metabolomics approach has not yet been explored in the search for biomarkers of peritoneal and deep infiltrating endometriosis, but was successfully used in ovarian disease by our group (Vouk 2012). The results of the project J3-6799 will strengthen the significance of metabolomics in the field of biomarker discovery and pathophysiology of endometriosis. The project identified novel metabolites as biomarkers of endometriosis, and pinpointed the disturbed molecular processes and novel drug targets and may thus in a long term contribute to earlier diagnosis and treatment and concurrently decreased infertility and also to a better understanding of the pathophysiology of this intriguing disease. The novelties of the project are as follows: 1) use of metabolomics approach in peritoneal and deep infiltrating endometriosis; 2) biomarker discovery and validation phases followed by extensive and sound statistical analysis, and 3) development of algorithms for detection of endometriosis for further clinical validation.
Significance for the country
Slovenia has one of the lowest birth rates in Europe; therefore diagnosis and treatment of endometriosis, which has been detected in 40-50% of infertile patients, is of immense relevance for our country. The results of the project were published or will be submitted to high impact factor journals. The results were presented at several international scientific conferences thus contributing to international affirmation and promotion of Slovenia and Slovenian science. The research project enabled transfer of the cutting-edge knowledge of metabolomics to Slovenia. With the results and the knowledge gathered the project also enhanced the quality of research work as well as the quality of teaching at the Faculty of Medicine of the University of Ljubljana where it was performed. The knowledge stemming from this project was disseminated to medical students of the University of Ljubljana the Faculty of Medicine also through teaching class Hormone Dependent Gynecological Diseases: Clinical and Molecular Aspects (led by A. Vogler, S. Smrkolj and T. L. Rižner). In the framework of this research project Ph.D. student and several postdoctoral researchers were trained in state-of-the-art methods for the identification of biomarkers. The good results stemming from this project helped the collaborating institutions Medical Faculty at University of Ljubljana and University Medical Centre Ljubljana in terms of international recognition, competitiveness, and broadening collaborations for conducting larger studies within European and non-European partners.
Most important scientific results
Annual report
2014,
2015,
final report
Most important socioeconomically and culturally relevant results
Annual report
2014,
2015,
final report
