Metabolomic Insights Into Saliva as a Non-Invasive Surrogate for Serum to Enable Community-Based Biomarker Investigation.

[INTRODUCTION] Using serum metabolomics in Community-Based Participatory Research (CBPR) with underserved populations presents challenges due to the invasive nature of venipuncture, which limits longitudinal sample collection in community settings. In this pilot study, we compared saliva and serum metabolomics in patients with prostate cancer to evaluate saliva's potential in biomarker research and identified metabolic changes associated with androgen deprivation therapy (ADT).

[METHODS] Blood and saliva were collected from 20 eugonadal patients with prostate cancer and 20 patients receiving ADT. Untargeted metabolomics of metabolites was performed, and glucocorticoids were quantified using targeted metabolomics. Data were analyzed using MassHunter, METLIN database, and MetaboAnalyst.

[RESULTS] Across all samples, 1198 metabolites were identified. Comparing ADT to eugonadal serum and integrating fold change (FC > 2 or FC < 0.5) and significance (adjusted p < 0.1), we identified 14 upregulated and 20 downregulated metabolites. Comparing ADT to eugonadal saliva, we identified 14 upregulated and 28 downregulated metabolites. Targeted metabolomics confirmed correlations between serum and salivary cortisol and salivary and serum cortisone (r = 0.61 and 0.62, p < 0.001), underscoring the potential of saliva glucocorticoids as biomarkers for stress-related metabolic alterations and suggesting that saliva reflects the systemic metabolomic profile.

[CONCLUSION] ADT-associated metabolomic changes are detectable in saliva. Targeted analysis suggests that salivary glucocorticoids may serve as biomarkers of metabolism and stress in community-based studies. Our findings support saliva as a non-invasive alternative to serum for biomarker research, facilitating community-based investigations and advancing public health efforts.