Detecting endometriosis using peripheral blood

Non-invasive Diagnosis of Endometriosis

Key Points

Highlight:

• This review article describes latest studies on non-invasive biomarkers for the diagnosis of endometriosis.

Importance:

• A non-invasive biomarker-based test that can shorten the diagnostic delay for endometriosis will be highly useful.

What's done here:

• The authors presented an overview of recent biomarker studies in peripheral blood and endometrium.

Data:

• The most investigated biomarker was based on peripheral blood source.
• Hypothesis-driven biomarker discovery examined areas relating to the pathogenesis of endometriosis such as inflammation proteins and cytokines, oxidative stress markers, immune markers, autoimmune markers, endometrial cell survival/adhesion and migration markers, and pain-related markers.
• Hypothesis-generating approach has used the “omics” technologies for biomarkers discovery; however, biomarker validation remains challenging.
• Although a variety of biomarkers have been studied, no biomarker has been validated for clinical use in endometriosis.
• Future large-scale and highly powered studies will be needed.

Lay Summary

Laparoscopic visualization of endometriotic lesions with histological confirmation is the gold standard for the diagnosis of endometriosis. However, this diagnostic procedure, due to the need for laparoscopy and variability of disease/symptoms, can have a major delay up to 8-10 years from symptoms onset time. Another method such as transvaginal ultrasound is useful for deep nodules and ovarian endometriotic cysts identification, but it is dependent on the operator and has limited accuracy for the detection of superficial peritoneal lesions. Therefore, a non-invasive biomarker with high accuracy is an attractive avenue to the diagnosis of endometriosis.  

Dr. D'Hooghe et al. from Department of Development and Regeneration, Organ Systems, Leuven, Belgium recently published a review article in Best Practice & Research Clinical Obstetrics and Gynaecology journal to provide an overview of recent biomarkers for endometriosis diagnosis and the challenges on bringing these markers to the clinical practice.

Peripheral blood analysis was a useful source of biomarkers because it can be obtained with a minimally invasive procedure. Some biomarkers from peripheral blood that have been studied include cytokines and inflammatory, oxidative stress, immune/autoimmune and pain-related markers.

Cytokines and inflammatory proteins studied previously were (i) CA-125, a marker of peritoneal inflammation, though it is mostly elevated in advanced stages with poor specificity as it is elevated in other gynaecological diseases; (ii) IL-6, a pro-inflammatory cytokine, suffered from major problem with low detection of endometriosis serum; (iii) IL-35, an inhibitory cytokine, was upregulated in patients with endometrioma versus controls with infertility or benign ovarian tumours; (iv) YKL-40, inflammatory protein, significantly higher in women with endometriosis than in fertile controls; (v) circulating cell-derived microparticles, elevated in stage 3-4 and deeply infiltrative endometriosis; and (vi) soluble tumour necrosis factor receptor I (sTNFR-I) and sTNFR-II, significantly higher in women with all-stage endometriosis.

Oxidative stress markers discussed were total and active levels of myeloperoxidase (MPO), which showed a difference comparing women with endometriosis and those with benign gynecological disorders and others including superoxide dismutase (SOD) and glutathione peroxidase (GPx), in which diagnostic value was unclear.

Immune markers studied so far included Galectin-9, an immunomodulatory protein, which showed limited diagnostic accuracy. Other autoimmune markers such as autoantibodies, by using a panel of 6 autoantibodies (anti-tropomodulin (TMOD)3b, anti-TMOD3c, anti-TMOD3d, anti-tropomyosin (TPM)3a, anti-TPM3c and anti-TPM3d) showed promising results, although required further external independent validation.

Pain-related marker (plasma brain-derived neurotrophic factor) was able to discriminate between women with endometrioma and those with benign gynecological disorders but was not able to detect peritoneal endometriosis or deeply infiltrative endometriosis. Other sources, such as circulating endometrial cells were found at higher frequency in peripheral blood of endometriosis, but currently, there has been no reliable quantification method for these cells.

Non-hypothesis-driven approach to biomarker discovery often involved “omics” methods, including proteomics, sequencing and mRNA microarray. Although this approach may carry the added benefit of panel biomarker discovery to increase selectivity and specificity, they often suffered from validation challenges, due to high complexity regarding specific criteria for patient selection, methodology, and analysis.

In summary, a panel of biomarkers system is likely necessary to diagnose endometriosis. Thorough biomarker validation in an independent cohort remains crucial to develop a clinically useful non-invasive test.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29778458