Chronic Stress and Vaginal Fluid Metabolomics Signatures in Ovarian Cancer

This K22 proposal aims to enhance the applicant’s prior quantitative training through a combination of formal coursework and informal mentorship, supporting their transition to independence as a molecular cancer epidemiologist investigating biological mechanisms underlying disparities in female cancers. Ovarian cancer (OC), the deadliest gynecological malignancy, exhibits marked differences in outcomes that are not fully explained by clinical or socioeconomic factors. Chronic stress—an embodiment of adverse social conditions—has emerged as a potential contributor to these disparities through its influence on biological systems, including the vaginal microbiome. The vaginal microbiome can shape the tumor microenvironment via production of pro-carcinogenic metabolites and reduction of antineoplastic metabolites. Its composition and function are influenced by host factors and social determinants, including chronic stress exposure. Despite growing evidence linking microbiome-related inflammation to cancer progression, no studies have evaluated how chronic stress may alter vaginal fluid metabolite profiles and metabolic signatures in OC patients, nor how these changes may relate to disease aggressiveness and recurrence. Guided by ecosocial theory, which posits that adverse living and working conditions are literally biologically incorporated leaving bodily marks, this study will apply an untargeted metabolomics approach to analyze cervicovaginal fluid from 120 OC patients, with detailed assessment of chronic stress exposure at both individual and neighborhood levels. The specific aims are to: i). Characterize vaginal fluid metabolite profiles and metabolic signatures among OC patients, ii). Assess differences by chronic stress in vaginal fluid metabolite profiles and metabolic signatures among OC patients, and iii). Evaluate the relative importance of vaginal fluid metabolites and chronic stress on OC aggressiveness and recurrence. Completion of the proposed K22 will advance scientific understanding of how chronic stress and vaginal microbiome-derived metabolites contribute to OC progression. This knowledge may inform the development of prognostic biomarkers and therapeutic strategies targeting microbiome-mediated pathways. Clinically, the study may support the integration of vaginal metabolite profiling into personalized care approaches for OC patients. The proposed training and research will equip the applicant with the skills and resources necessary to establish an independent research program in molecular cancer epidemiology.