Serological proteomic profiling uncovered CDK5RAP2 as a novel marker in benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) affects approximately half of men over the age of 50. Early detection and timely treatment facilitate disease intervention and achieve a better clinical outcome. However, current clinical methods, such as prostate specific antigen (PSA), lack the sensitivity to accurately distinguish between BPH and prostate cancer (PCa). Thus, optimal serum markers are warranted to complement existing diagnostic tests. In this study, we recruited 1987 BPH patients and characterized their clinical features. To explore BPH proteomic alterations, a data independent acquisition-based mass spectrometry proteomics approach was adopted for 66 serum samples from healthy males (n = 22), patients with BPH (n = 22) and prostate cancer (n = 22). Bioinformatic evaluations were performed for proteomic profiling and candidate selection. In addition, a promising candidate was further validated with ELISA assay. Our findings revealed that the level of free PSA correlated with prostate volume. 7.95 % of BPH patients had a PSA value greater than 10 ng/mL, with elevated free PSA, prostate volume, PSA density, and decreased free to total PSA ratio. Mass spectrometry-based serum profiling demonstrated distinct differences between BPH and PCa. CDK5RAP2 was weighted most important in BPH patients' serum and achieved an area under the receiver operating characteristic curve of 0.900 in distinguishing BPH and PCa, which was further validated by publicly-available mRNA microarray analysis and cellular phenotype evaluation. Our comprehensive analysis systematically explored BPH serum characteristics, proteomic profiles, and identified novel serum markers that may contribute to the understanding of BPH and facilitate early diagnosis and intervention.