Patient-derived prostate organoids identify MAOA as a disease severity-associated molecular marker in chronic pelvic pain syndrome

Abstract

Abstract Chronic pelvic pain syndrome (CPPS) is a multifactorial condition with unclear pathophysiology and a lack of objective biomarkers for assessing disease activity. To investigate its molecular basis, we generated patient-derived prostate organoids from biopsy tissues of nine patients with CPPS, categorized as mild, moderate, or severe according to the NIH CP Symptom Index scores. The organoids were treated with Eviprostat or tadalafil, followed by transcriptomic profiling, quantitative RT-PCR validation, and immunohistochemical analysis of candidate genes. Among the differentially expressed genes, monoamine oxidase A (MAOA) and calbindin-D28K (CALB1) were consistently associateds with symptom severity. Expression of both genes decreased in organoids and prostate tissues as symptom severity increased, whereas serum MAOA levels were significantly elevated in patients with severe CPPS. These findings suggest that MAOA and CALB1 reflect molecular alterations linked to symptom intensity and may serve as potential biomarkers for CPPS. Furthermore, patient-derived prostate organoids offer a valuable experimental platform for elucidating disease mechanisms and evaluating therapeutic interventions in prostatitis-related disorders.