Racial Differences in Vaginal Fluid Metabolites and Association with Systemic Inflammation Markers among Ovarian Cancer Patients: A Pilot Study

Author:

Osazuwa-Peters Oyomoare L.1ORCID,Deveaux April1,Muehlbauer Michael J.2,Ilkayeva Olga23ORCID,Bain James R.23ORCID,Keku Temitope4,Berchuck Andrew5,Huang Bin6,Ward Kevin7,Gates Kuliszewski Margaret8,Akinyemiju Tomi19ORCID

Affiliation:

1. Department of Population Health Sciences, Duke University School of Medicine, Durham, NC 27701, USA

2. Duke University School of Medicine, Duke Molecular Physiology Institute, Durham, NC 27701, USA

3. Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA

4. Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

5. Duke Division of Gynecologic Oncology, Duke University School of Medicine, Durham, NC 27710, USA

6. Kentucky Cancer Registry, University of Kentucky, Lexington, KY 40506, USA

7. Georgia Cancer Registry, Emory University, Atlanta, GA 30322, USA

8. New York State Cancer Registry, New York State Department of Health, Albany, NY 12204, USA

9. Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA

Abstract

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50–70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1β, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.

Funder

National Institutes of Health/National Cancer Institute

NIH

USDA

Publisher

MDPI AG

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