Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 2 3 2024 09 25 132 138 Jamal Amri 1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R, Iran. Davood Goodarzi Department of Urology, Faculty of Medicine, Arak University of Medical Sciences, Arak, IR Iran Mona Alaee 2. Students’ Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, I.R, Iran. Mohammadreza Zarei 1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R, Iran. Mehdi Salehi Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran. 2025 05 23 Objectives: Early detection of prostate disease is crucial, but current methods have limitations.  S100P protein and saliva sampling offer potential non-invasive diagnostic options.  This study aimed to evaluate S100P and PSA as biomarkers for prostate cancer (PC) and differentiate PC from benign prostatic hyperplasia (BPH).  Additionally, the study investigated the suitability of saliva as a diagnostic medium for prostate patients. Methods: This case-control study included 100 Iranian men aged 50 to 65 years, divided into two groups: 50 men with PC and 50 men with BPH. Serum and saliva samples were collected from each patient after a consent form was obtained. Serum and salivary PSA and S100P levels were measured using ELISA kits.  Mann–Whitney U test, Spearman’s correlation coefficients and receiver operating characteristic (ROC) analysis were applied to evaluate the data. Results: Salivary and serum PSA and S100P levels were significantly higher in men with PC compared to those with BPH (P<0.001). A strong positive correlation was observed between serum and salivary levels of both biomarkers in two groups (P<0.001). ROC curve analysis indicated that salivary PSA and S100P levels could effectively differentiate PC from BPH.   Conclusions: Salivary PSA and S100P hold promise as non-invasive biomarkers for PC detection and differentiation from BPH. Further research with larger cohorts is needed to validate these findings and confirm the clinical utility of salivary PSA and S100P in PC and BPH diagnosis and management. https://abi.tums.ac.ir/index.php/abi/article/view/118 https://abi.tums.ac.ir/index.php/abi/article/download/118/66