Abstract 1929: Metabolomic insights into androgen deprivation therapy, and saliva as a non-invasive surrogate for serum to enable community-based biomarker studies

Abstract Introduction: Androgen deprivation therapy (ADT) significantly alters metabolism in prostate cancer patients. Serum metabolomics are the gold standard for studying these effects; however, saliva offers a non-invasive alternative for biomarker assessment. This study evaluates the impact of ADT on serum and saliva metabolites and the correlation between the two matrices. By evaluating saliva as a potential surrogate for serum, this work explores its application in biomarker analysis of chronic risk factors within community health programs. Methods: Blood and saliva were collected from 20 eugonadal men and 20 men receiving hormonal therapy for prostate cancer, and were processed per standard protocols and stored at -80°C. Untargeted metabolomics using UPLC-MS analysis of polar and non-polar metabolites were performed; and glucocorticoids were quantified using targeted LC-MS/MS. Data were analyzed using MassHunter, METLIN database, and MetaboAnalyst, with log-transformation and by Mann-Whitney tests (False Discovery Rate (FDR)-adjusted P-values < 0.05). Results: In untargeted metabolomics, 1, 198 metabolites were identified across serum and saliva. Comparing ADT to eugonadal serum, 35 metabolites had fold-changes (FC)>2 and 35 had FC<0.5, with 248 metabolites reaching statistical significance (adjusted-P<0.05). Similarly, in saliva, 54 metabolites had FC>2 and 69 had FC<0.5, with 82 metabolites showing significant differences (P<0.05). Comparing serum to saliva across all participants, 248 metabolites had FC>2 and 268 had FC<0.5, with 697 reaching statistical significance (P<0.05). When integrating fold changes (FC>2 or FC<0.5) and significance thresholds (adjusted-p<0.1), we identified 14 upregulated and 20 downregulated metabolites in serum, and 14 upregulated and 28 downregulated metabolites in saliva of ADT patients compared to eugonadal patients; and 247 upregulated and 268 downregulated metabolites in saliva compared to serum among participants. Targeted metabolomics also confirmed strong correlations between serum and salivary cortisol (r=0.612, p<0.001) and cortisone (r=0.618, p<0.001). These findings underscore the potential of glucocorticoids as biomarkers for stress-related metabolic alterations, suggesting that saliva potentially reflects the systemic metabolomic profile. This highlights saliva’s promise for non-invasive biomarker studies in stress and broader community health applications. Conclusion: ADT is associated with significant changes in serum and salivary metabolome, highlighting its systemic and local impact on metabolism. Moreover, targeted metabolomic analysis revealed strong correlations between glucocorticoids in serum and saliva, suggesting saliva may serve as a non-invasive surrogate for serum in biomarker studies to facilitate research in community health programs. Citation Format: Alireza Abdshah, Mohammad Alyamani, Marijo Bilusic, Dipen J. Parekh, Benjamin Spieler, Rakesh Singal, Brandon A. Mahal, Erin Kobetz, Sanoj Punnen, Matthew C. Abramowitz, Jaime R. Merchan, Nima Sharifi. Metabolomic insights into androgen deprivation therapy, and saliva as a non-invasive surrogate for serum to enable community-based biomarker studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1929.