Effects of Clinical Covariates on Serum miRNA Expression among Women without Ovarian Cancer.

Background: Serum miRNAs are potential biomarkers for ovarian cancer; however, many factors may influence miRNA expression. To understand potential confounders in miRNA analysis, we examined how sociodemographic factors and comorbidities, including known ovarian cancer risk factors, influence serum miRNA levels in women without ovarian cancer.

Methods: Data from 1,576 women from the Mass General Brigham Biobank collected between 2012 and 2019, excluding subjects previously or subsequently diagnosed with ovarian cancer, were examined. Using a focused panel of 179 miRNA probes optimized for serum profiling, miRNA expression was measured by flow cytometry using the Abcam FirePlex assay and correlated with subjects' electronic medical records.

Results: The study population broadly reflected the New England population. The median age of subjects was 49 years, 34% were current or prior smokers, 33% were obese (body mass index > 30 kg/m2), 49% were postmenopausal, and 11% had undergone prior bilateral oophorectomy. Significant differences in miRNA expression were observed among ovarian risk factors such as age, obesity, menopause, BRCA1 or BRCA2 germline mutations, or existence of breast cancer in family history. Additionally, miRNA expression was significantly altered by prior bilateral oophorectomy, hypertension, and hypercholesterolemia. Other variables, such as smoking; parity; age at menarche; hormonal replacement therapy; oral contraception; breast, endometrial, or colon cancer; and diabetes, were not associated with significant changes in the panel when corrected for multiple testing.

Conclusions: Serum miRNA expression patterns are significantly affected by patient demographics, exposure history, and medical comorbidities.

Impact: Understanding confounders in serum miRNA expression is important for refining clinical assays for cancer screening.