Shoskes Daniel A, Keslar Karen S, Gotwald Paige, Berglund Ryan, Vij Sarah
Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH, USA.
Transl Androl Urol. 2021 Aug;10(8):3340-3347. doi: 10.21037/tau-21-387.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has diverse clinical phenotypes and its etiology is multifactorial. Studies to date of gene expression in humans have been limited to small numbers of target genes. NanoString can simultaneously measure hundreds of genes. We wished to study gene expression in blood and urine of CP/CPPS patients compared to controls for neuroinflammatory genes and characterize the results by patient phenotype.
Blood and urine were collected from 10 men with CP/CPPS and 7 asymptomatic controls. RNA was isolated from urine pellets using Qiagen RNeasy kits. Whole blood was collected and RNA isolated. 100 ng of RNA was used for gene expression analysis with the 770-gene NanoString Human Neuroinflammation gene panel. Data was imported into Rosalind (OnRamp Bioinformatics) for normalization, calculation of fold-changes and P values, and identification of enriched pathways. Gene expression was considered significantly different if there was a greater than 1.5× change compared to controls and corrected P was <0.05.
Mean patient age was 42.2 years, median symptom duration was 15.5 months, median UPOINT domains was 3 and mean total National Institute of Health-Chronic Prostatitis Symptom Index Score was 28.8. In blood, there were 5 genes with significantly different expression to controls, the largest differences found in FOS1 (neuropathic pain control), PROS1 (blood clotting) and DDX58 (antiviral innate immunity). Gene set analysis showed differences in inflammation, angiogenesis and cytokine signaling. In urine there were 48 genes with significantly different expression including SLAMF8 (lymphocyte activation) and LAIR1 (inhibits B and T cell function). Gene set analysis showed differences in carbohydrate metabolism, neurons and neurotransmission, adaptive immunity and inflammatory signaling. Subgroup analysis by UPOINT domain showed unique gene expression in the Organ Specific and Neurologic/Systemic domains in both blood and urine for neurogenic pain and cytokine signaling associated genes.
Men with CP/CPPS have a diverse set of neuroinflammatory genes with differential expression compared to controls. Clinical phenotypes have distinct patterns of gene expression. These findings could lead to novel biomarker development, emphasize the importance of multimodal therapy targeting diverse pathways and further validate the biologic basic of clinical phenotyping.
慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS）具有多种临床表型，其病因是多因素的。迄今为止，人类基因表达研究仅限于少数目标基因。NanoString技术可以同时检测数百个基因。我们希望研究CP/CPPS患者血液和尿液中神经炎症基因的表达，并与对照组进行比较，同时根据患者表型对结果进行特征分析。
收集10例CP/CPPS男性患者和7例无症状对照者的血液和尿液。使用Qiagen RNeasy试剂盒从尿沉渣中提取RNA。采集全血并提取RNA。将100 ng RNA用于770基因的NanoString人类神经炎症基因检测板进行基因表达分析。数据导入Rosalind（OnRamp生物信息学）进行标准化、倍数变化计算和P值计算，并识别富集通路。与对照组相比，如果变化大于1.5倍且校正后的P值<0.05，则认为基因表达存在显著差异。
患者平均年龄为42.2岁，症状持续时间中位数为15.5个月，UPOINT域中位数为3，美国国立卫生研究院慢性前列腺炎症状指数总分平均为28.8。在血液中，有5个基因的表达与对照组有显著差异，差异最大的是FOS1（神经性疼痛控制）、PROS1（血液凝固）和DDX58（抗病毒先天免疫）。基因集分析显示炎症、血管生成和细胞因子信号传导存在差异。在尿液中，有48个基因的表达有显著差异，包括SLAMF8（淋巴细胞激活）和LAIR1（抑制B和T细胞功能）。基因集分析显示碳水化合物代谢、神经元和神经传递、适应性免疫和炎症信号传导存在差异。按UPOINT域进行亚组分析显示，在血液和尿液中，器官特异性和神经/全身域中与神经源性疼痛和细胞因子信号传导相关的基因存在独特的基因表达。
与对照组相比，CP/CPPS男性患者有多种神经炎症基因存在差异表达。临床表型具有独特的基因表达模式。这些发现可能会导致新的生物标志物的开发，强调针对多种通路的多模式治疗的重要性，并进一步验证临床表型的生物学基础。
