Can a Gene Expression Signature Help Diagnose Endometriosis?

Jake Remaly

December 01, 2020

A gene expression signature may help physicians diagnose endometriosis by analyzing samples from endometrial biopsies instead of relying on more invasive methods, research suggests.

Yana B. Aznaurova, MD, and colleagues identified and validated a genetic biomarker based on differences in the endometrium of women with and without endometriosis. The biomarker is based on five genes that were down-regulated in patients with the disease.

Endometriosis is an enigmatic gynecologic disease that is associated with chronic pelvic pain, dyspareunia, and dysmenorrhea, said Aznaurova, of the department of reproductive medicine and surgery at A.I. Evdokimov Moscow State Medical and Dental University. Laparoscopy with histological confirmation is the standard method of diagnosis.

"Development of minimally invasive or even noninvasive diagnostic tests is a research priority in endometriosis," she said at the meeting sponsored by the American Association of Gynecologic Laparoscopists, held virtually this year.

Attempts to identify biomarkers have tended to focus on single genes or proteins, but "endometriosis is a ... multifactorial disease," said Aznaurova. Researchers have found that signaling pathway activation profiles are a more stable and reliable marker of some diseases.

To validate a complex gene expression biomarker for the diagnosis of endometriosis, the researchers conducted an observational cohort study that included 50 women with endometriosis and 35 controls. The patients with endometriosis were 18-49 years old, had not received hormone therapy in the past year, and did not have other gynecologic diseases. Patients in the control group had uterine scar incompetence after cesarean section, but did not have endometriosis or other gynecologic disease.

Investigators performed RNA sequencing of endometrial samples, including 50 eutopic and 50 ectopic samples from patients with endometriosis, and 35 samples from patients in the control group.

They analyzed gene expression and intracellular pathway activation profiles to identify an endometrial gene expression signature that differentiated samples from patients with and without the disease, with an area under the receiver operating characteristic curve of approximately 0.99.

The researchers further studied the biomarker using preexisting datasets with 120 other tissue samples, including from the cervix, ovarian surface epithelium, stomach, and lung. The biomarker had a sensitivity of 94% and specificity of 97% for endometriosis in these analyses.

The results suggest that the genetic biomarker "could be potentially used as a basis for early diagnosis of endometriosis via utilization of endometrial biopsy only," Aznaurova said.

Further studies are needed to validate these findings, she noted.

"If we had a noninvasive way to look for endometriosis, this would be very powerful – very important as potentially a diagnostic test, or a triage test, or a monitoring test of treatment," Patrick P. Yeung Jr., MD, said in a discussion following Aznaurova's presentation.

The test might even suggest a target for treatment, said Yeung, professor of obstetrics, gynecology, and women's health at Saint Louis University.

Aznaurova and Yeung had no relevant financial disclosures.

SOURCE: Aznaurova YB et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.040.

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