Non-invasive clinical markers for diagnosis of endometriosis

Project Information

GLYCOMENDO

Grant agreement ID: 843862

DOI

10.3030/843862

Project closed

EC signature date 10 April 2019

Start date 2 September 2019

End date 1 September 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 196 590,72

EU contribution

€ 196 590,72

Coordinated by

NATIONAL INSTITUTE FOR BIOPROCESSING RESEARCH AND TRAINING LIMITED
Ireland

Periodic Reporting for period 1 - GLYCOMENDO (Non-invasive clinical markers for diagnosis of endometriosis)

Reporting period: 2019-09-02 to 2021-09-01

Summary of the context and overall objectives of the project

What is the problem/issue being addressed?
Endometriosis is a chronic disease of poorly understood pathomechanism and highly limited diagnostic techniques. It is characterised by the growth of endometrial-like tissue outside the uterine cavity affecting 6-10% of childbearing-aged women. The invasive laparoscopic surgery can provide a definitive diagnosis of endometriosis though causes a significant delay in the recognition and management of the disease. Therefore, in collaboration with clinicians, we recruited patients to participate in this study. The participants contributed to the collection of blood, urine, and high vaginal swab samples during their laparoscopic surgery. Blood and urine as minimally or non-invasive sample sources are ideal candidates for the development of new diagnostic methods. In the first year of the Glycomendo project, glycome characterization of urine of endometriosis patients was performed. As part of this work, we developed a new protocol for the pre-processing of urine samples and then characterized the glycan composition of the urine by mass spectrometry and high-performance liquid chromatography (HPLC).

Why is it important for society?
Despite the prevalence of endometriosis, the aetiology of the disease is still poorly understood. In addition, endometriosis causes fertility problems and reduced quality of life and this enigmatic disease also has a serious economic cost. Direct healthcare costs for women with endometriosis are more than twice as high as women without the disease. A future minimally or non-invasive diagnostic technique would allow for an earlier diagnosis of endometriosis. This could reduce patients’ hospitalization costs and time, which is also beneficial for the economic burden, and would improve patients' well-being.

What are the overall objectives?
The purpose of the Glycomendo project is to identify diagnostic candidates that could replace invasive laparoscopic surgery with non-invasive diagnostic technique in the future. We also would like to draw society's attention to this little-known disease, which affects many women so that those concerned can receive appropriate medical care as soon as possible.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the first year of the Glycomendo project, the focus was on developing the methods needed to carry out the project. During the work, a urine pre-processing protocol was developed that allows enzymatic digestion and further analysis of N-linked glycans. There are optimized automated high-throughput protocols developed in our group for whole serum glycan and IgG capture from the serum samples. The whole urinary N-glycome profile is unknown in literature. We are doing characterisation of the whole urine N-glycome based on exoglycosidase digestions, ultra performance liquid chromatography (UPLC) and mass spectrometry (MS) data of pooled urine samples. We have developed IgG capture method from the urine samples. Optimization is also required in case of urinary IgG capturing because its’ IgG concentration is close to the detection limit, which is an ongoing project.
In addition to method developing, Zsuzsanna Kovács (ZK) regularly participated in laparoscopic surgeries (before COVID-19 pandemic), where she had the opportunity to learn about the disease from clinical colleagues and to gain experience of the variety of manifestations of the disease. Patients also had the opportunity to communicate with ZK and get information about the Glycomendo project. ZK is in close contact with the local charity of the Endometriosis Association of Ireland and helps to spread information about endometriosis for the laic audience.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

As a summary of the literature search, ZK wrote a review article in collaboration with clinical colleagues and her PI, Radka Fahey Saldova (RFS). This manuscript in question had been submitted to a Q1 journal and currently waiting for feedback information about it.
Urinary N-glycome is unknown in literature and the urinary protocol for N-glycan release could have a high impact on biomarker research in other diseases as the urine is a great source of non-invasive biomarker candidates mainly in renal or haematological related diseases (kidney failure caused by multiple myeloma, diabetes mellitus type I and II etc.).
The Glycomendo project considers it a priority to make the widest possible audience aware of endometriosis and its therapeutic options. Dissemination of information about the Glycomendo project and its objectives, as well as the disease, takes place through several forums. ZK is in close contact with the charity of Endometriosis Association of Ireland and have created an own Twitter page and website for the Glycomendo project and are also included in the profiles of the participating researchers (ZK and RFS) as a ResearchGate project. On the Twitter page of the Glycomendo project, we frequently share interesting news and events related to endometriosis which helps spread the latest news. In addition, the Glycomendo website is a bilingual online surface and all information is available in English and Hungarian. As ZK is aware of lack of information in Hungarian and she committed to improving this situation and the first step was a Hungarian website as well she contacted the administrator of Hungarian Endometriosis Association.

Sources of non-invasive biomarker candidates