AUTHOR=He Jinhua , Han Zeping , Luo Wenfeng , Shen Jian , Xie Fangmei , Liao Liyin , Zou Ge , Luo Xin , Guo Zhonghui , Li Yuguang , Li Jianhao , Chen Hanwei 

TITLE=Serum organic acid metabolites can be used as potential biomarkers to identify prostatitis, benign prostatic hyperplasia, and prostate cancer

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.998447

DOI=10.3389/fimmu.2022.998447

ISSN=1664-3224

ABSTRACT=Background：Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia(BPH), and prostate cancer(PCa) are current clinical challenges. Methods：The serum metabolites of 20 healthy individuals and patients with prostatitis , BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS). Results：Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D-glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy-3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (AUC=0.750), and pyroglutamic acid (AUC=0.929). Conclusions：These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa.