Could the cell surface protein "EWI-2" be the new diagnostic marker for endometriosis?

A cell surface protein and an early activation marker, EWI-2 gene expression is downregulated in patients with endometriosis compared to those without.

Key Points

Highlights:

Investigation of the EWI-2 gene, a cell surface protein and an early activation marker (also known as IGSF8), from patients with histologically proven endometriosis, has shown that EWI-2 gene expression is downregulated.

Importance: 

The EWI-2 gene could be useful as a diagnostic biomarker and therapeutic target in the future.

Key Results:

• EWI-2 expression was not significantly different among healthy women in the different phases of the menstrual cycle. [Proliferative phase of the menstrual cycle is the estrogenic phase during which ovarian follicles develop and mature in preparation for ovulation; while in secretory phase endometrium is under progesterone effect]. However, in women with endometriosis, the secretory phase was marked by a decreased EWI-2 expression compared to the proliferative phase.

• Compared to control (healthy) endometrium tissue samples, samples collected from women with endometriosis revealed a significantly decreased expression of EWI-2 in all phases of the cycle.

• Statistical analysis (Receiver under the operator curve, ROC analysis) revealed that EWI-2 expression in all stages of the menstrual cycle could be used as a diagnostic tool.

• EWI-2 inhibits the migration and invasion of endometrial epithelial cells via negative regulation of the PI3K/Akt axis.

• Decreasing the EWI-2 gene expression by genetic knockout techniques increases the ability of endometriotic cells to migrate and invade adjacent tissues.

What’s done here?

This study has investigated the differential expression of EWI-2 in normal endometrium and endometriosis tissues and assessed its potential use as a diagnostic marker. While this study offers suggestive evidence of the role of EWI-2 in the pathogenesis of endometriosis, further clinical studies are warranted to fully assess and validate its use as a screening and therapeutic target.

Lay Summary

Further Understanding:

Researchers from the Reproductive Medicine Center of Wuhan University sought to observe the differential expression of EWI-2, (a cell surface protein and an early activation marker, also known as IGSF8 - Immunoglobulin superfamily member 8) in 145 women affected by endometriosis through their normal and ectopic endometrium (endometriosis). Additionally, they compared the EWI-2 levels in varying phases of the menstrual cycle.

The researchers aimed to understand if the levels of this gene could be used as a predictive marker for endometriosis. Analysis of EWI-2 expression among healthy women in the proliferative or secretory phases of the menstrual cycle revealed no significant difference. However, among women with endometriosis, the secretory phase was marked by a decreased EWI-2 expression compared to the proliferative phase. Additionally, compared to control (healthy) endometrium tissue samples, samples collected from women with endometriosis revealed a significantly decreased expression of EWI-2. 

Statistical analysis revealed that EWI-2 mRNA expression in all stages of the menstrual cycle could be used as a diagnostic tool to identify individuals that may be affected by endometriosis. Furthermore, EWI-2 expression in stage-matched ectopic and eutopic lesions revealed that in the early, middle, and late secretory phase, ectopic endometrial tissues expressed higher amounts of EWI-2 mRNA than their normal endometrium tissues.

This recently published study has led to the understanding of differential expression patterns in women with endometriosis and that EWI-2 may be useful diagnostically to separate those with or without endometriosis.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28544021