Ectoenzymes as endometriosis biomarkers

Ectoenzymes as endometriosis biomarkers

Candidate endometriosis biomarkers: ADA and ENPP1

Key Points


  • Endometriosis diagnosis is usually delayed because there is a lack of biomarkers or non-invasive diagnostic tests. Would it be possible to use extracellular enzymes for early diagnosis of endometriosis?


  • The ectoenzymes (extracellular enzymes) including adenosine deaminase (ADA) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) are biomarker candidates for endometriosis.

What's done here:

  • A case-control comparative study which compares the levels of the ectoenzymes in aspirated fluids of endometriomas (case group, n=19) and simple ovarian cysts (control group, n=47) using ELISA technique.
  • Evaluated ectoenzymes are ADA, alkaline phosphatase (ALP), ENPP1, and ENPP3 in aspirated fluids of endometriomas, which are part of the cell signaling and commonly altered in many inflammatory disorders.


  • ADA, ALP, ENPP1, and ENPP3 were detected in fluids collected from endometriomas and simple cysts.
  • ADA and ENPP1 levels were significantly higher in endometrioma contents than simple cysts.


  • The study is limited by the small number of endometriomas; future studies are necessary to validate the data.
  • The authors did not examine whether these enzymes were detectable in blood samples of women with endometriosis.
  • The diagnostic values, sensitivity and specificity of ADA and ENPP1 need confirmation and not simple cysts, but other inflammatory cystic diseases should be evaluated in the control arm.
  • It is an invasive manipulation to get the content of endometrioma; once it is removed surgically, the disease can be diagnosed histopathologically.

Lay Summary

The diagnosis of endometriosis is often delayed by 7 to 11 years because of the lack of a non-invasive diagnostic test. The ovarian endometriomas occur in about 17%-44% of women with endometriosis and cysts which contain endometrial tissue and fluid of blood from the accumulation of menstrual debris. This ovarian endometriomas fluid can be seen as a waste fluid. However, its analysis may help to identify new biomarkers for endometriosis.

The study by Trapero et al. analyzed the content of ovarian endometriomas by measuring the levels of extracellular enzymes (ectoenzymes) that are involved in purinergic signaling. This type of signaling response is essential in many inflammatory conditions during tissue stresses stimulated by hypoxia, necrosis and inflammation factors. It is present to protect cells and tissues from excessive immune/inflammation caused damage.

Since endometriosis is related to inflammation, the study aimed to determine ectoenzymes levels in purinergic signaling including adenosine deaminase (ADA), alkaline phosphatase (ALP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ENPP3 by using ELISA technique. This case-control study was compared the level of these enzymes in fluid from 19 ovarian endometriomas and 47 simple ovarian cysts. The data showed that these ectoenzymes were present in the aspirated fluids from both endometriomas and simple ovarian cysts. However, the levels of ADA and ENPP1 were significantly higher in endometrioma fluids as compared to other cyst fluids, while ALP and ENPP3 levels were not significantly different. This study suggests that analyzing the composition of endometrioma contents may derive candidate biomarkers useful for the diagnosis of endometriosis.

At this stage, the study is limited by a small number of ovarian endometriomas. Future studies examining a large cohort with data containing selectivity and specificity for clinical diagnosis will be necessary to determine the values of measuring ectoenzymes in ovarian endometriomas fluids. Analysis of blood samples from endometriosis patients may also help to understand the overall diagnostic utility of ectoenzymes better. Nonetheless, the study showed evidence linking purinergic signaling and endometriosis, expanding current understanding of endometriosis pathophysiology.

Research Source:

biomarker diagnosis Ectoenzymes endometriosis biomarkers extracellular enzymes


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