An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review
Résumé
Biomarker identification could help in deciphering endometriosis pathophysiology in addition to their use
in the development of non invasive diagnostic and prognostic approaches, that are essential to greatly improve
patient care. Despite extensive efforts, no single potential biomarker or combination has been clinically validated
for endometriosis.
Many studies have investigated endometriosis-associated biological markers in specific tissues, but an integrative
approach across tissues is lacking. The aim of this review is to propose a comprehensive overview of identified biomarkers
based on tissue or biological compartment, while taking into account endometriosis phenotypes (superficial,
ovarian or deep, or rASRM stages), menstrual cycle phases, treatments and symptoms.
We searched PubMed and Embase databases for articles matching the following criteria: ’endometriosis’ present
in the title and the associated term ’biomarkers’ found as Medical Subject Headings (MeSH) terms or in all fields. We
restricted to publications in English and on human populations. Relevant articles published between 01 January 2005
(when endometriosis phenotypes start to be described in papers) and 01 September 2022 were critically analysed
and discussed.
Four hundred forty seven articles on endometriosis biomarkers that included a control group without endometriosis
and provided specific information on endometriosis phenotypes are included in this review. Presence of information
or adjustment controlling for menstrual cycle phase, symptoms and treatments is highlighted, and the results are
further summarized by biological compartment. The 9 biological compartments studied for endometriosis biomarker
research are in order of frequency: peripheral blood, eutopic endometrium, peritoneal fluid, ovaries, urine, menstrual
blood, saliva, feces and cervical mucus. Adjustments of results on disease phenotypes, cycle phases, treatments
and symptoms are present in 70%, 29%, 3% and 6% of selected articles, respectively. A total of 1107 biomarkers were
identified in these biological compartments. Of these, 74 were found in several biological compartments by at least
two independent research teams and only 4 (TNF-a, MMP-9, TIMP-1 and miR-451) are detected in at least 3 tissues
with cohorts of 30 women or more.
Integrative analysis is a crucial step to highlight potential pitfalls behind the lack of success in the search for clinically
relevant endometriosis biomarkers, and to illuminate the physiopathology of this disease.
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