S100A12 correlates with inflammatory and pain symptoms in patients with chronic prostatitis/chronic pelvic pain syndrome

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Pain Pub Date : 2025-09-04 DOI:10.1016/j.jpain.2025.105536

Marc Manthey , Temuujin Dansranjav , Hang Yan , Adrian Pilatz , Hans-Christian Schuppe , Jens Rosellen , Heidrun H. Krämer , Elena Neumann , Florian Wagenlehner , Undraga Schagdarsurengin

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Abstract

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most prevalent urological condition in men under 50, characterized by persistent or recurrent pelvic and perineal pain, and significantly reduced quality of life. Reliable biomarkers for assessment and mechanistic understanding of pain remain limited. This retrospective case-control study consisting of 90 CP/CPPS patients (median age 29.4 years) and 90 age-matched healthy controls investigated the alarmin S100A12 as a potential biomarker linking inflammation to neurogenic pain. Seminal plasma, serum, and post-prostatic massage (PPM) urine samples were analyzed. S100A12 levels were significantly elevated in patients in seminal plasma (median 47.8 vs. 2.5 ng/ml, p<0.001) and serum (median 49.2 vs. 17.4 ng/ml, p<0.001). Seminal S100A12 correlated with inflammatory markers (ρ=0.551–0.686), CPSI pain scores (ρ=0.451, p<0.001), and IPSS (ρ=0.342, p=0.001). Receiver operating characteristic analysis demonstrated superior diagnostic performance for seminal S100A12 (AUC=0.90, 95% CI: 0.77–0.93) compared to leukocyte count (AUC=0.60), IL-8 (AUC=0.70), and granulocyte elastase (AUC=0.50). S100A12 also correlated with sperm tail defects (ρ=0.445, p<0.001), and inversely with motility (ρ=–0.306, p=0.003) and vitality (ρ=–0.273, p=0.005). In silico analysis of prostate single-cell RNA sequencing data identified S100A12-expressing CXCR1+ myeloid cells, suggesting a link to IL-8–mediated inflammation. PPM urine-derived leukocytes from patients showed increased expression of RAGE (p=0.006) and CALCA (p<0.001), correlating with pain severity (ρ=0.541, p<0.001). These findings implicate S100A12 in leukocyte–nerve interactions underlying pelvic pain and dysfunction, and support its use as a diagnostic biomarker and potential therapeutic target in CP/CPPS.

Perspective

This study identifies S100A12 as a potential biomarker of inflammation and pain in young CP/CPPS patients. The findings suggest a neuroimmune interaction involving S100A12, RAGE, and CGRP/NGF signaling, which may guide future patient stratification and therapeutic development targeting pain chronicity, inflammation, and reproductive dysfunction in CP/CPPS.

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S100A12与慢性前列腺炎/慢性盆腔疼痛综合征患者的炎症和疼痛症状相关

慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS）是50岁以下男性最常见的泌尿系统疾病，其特征是持续或复发性盆腔和会阴疼痛，生活质量显著降低。评估疼痛的可靠生物标志物和对疼痛机制的理解仍然有限。这项回顾性病例对照研究由90名CP/CPPS患者（中位年龄29.4岁）和90名年龄匹配的健康对照者组成，研究了警报蛋白S100A12作为连接炎症与神经源性疼痛的潜在生物标志物。分析精浆、血清和前列腺按摩后（PPM）尿液样本。患者精浆中的S100A12水平显著升高（中位值47.8 vs. 2.5 ng/ml, p<0.001）和血清中的S100A12水平显著升高（中位值49.2 vs. 17.4 ng/ml, p<0.001）。精液S100A12与炎症标志物（ρ= 0.551-0.686）、CPSI疼痛评分（ρ=0.451, p=0.001）和IPSS （ρ=0.342, p=0.001）相关。与白细胞计数（AUC=0.60）、白细胞介素8 （AUC=0.70）和粒细胞弹性酶（AUC=0.50）相比，受者工作特征分析显示精液S100A12 （AUC=0.90, 95% CI: 0.77-0.93）具有更好的诊断性能。S100A12也与精子尾部缺陷相关（ρ=0.445, p= 0.001），与活力（ρ= -0.306, p=0.003）和活力（ρ= -0.273, p=0.005）呈负相关。前列腺单细胞RNA测序数据的计算机分析鉴定出表达s100a12的CXCR1+髓样细胞，提示与il -8介导的炎症有关。患者PPM尿源性白细胞RAGE （p=0.006）和CALCA （p= 0.001）表达增加，与疼痛严重程度相关（p= 0.541, p= 0.001）。这些发现提示S100A12参与骨盆疼痛和功能障碍背后的白细胞-神经相互作用，并支持其作为CP/CPPS的诊断生物标志物和潜在治疗靶点的应用。本研究确定S100A12是年轻CP/CPPS患者炎症和疼痛的潜在生物标志物。研究结果提示，涉及S100A12、RAGE和CGRP/NGF信号的神经免疫相互作用可能指导未来CP/CPPS患者分层和针对疼痛慢性、炎症和生殖功能障碍的治疗开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pain 医学-临床神经学

CiteScore

6.30

自引率

7.50%

发文量

441

审稿时长

42 days

期刊介绍： The Journal of Pain publishes original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. Articles selected for publication in the Journal are most commonly reports of original clinical research or reports of original basic research. In addition, invited critical reviews, including meta analyses of drugs for pain management, invited commentaries on reviews, and exceptional case studies are published in the Journal. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals to publish original research.