Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients.

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients.
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DOI:
10.1002/pros.23439
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发表时间:
2018-01
期刊:
The Prostate
影响因子:
--
通讯作者:
Fowke JH
Fowke JH
中科院分区:
其他
文献类型:
--
作者:
Tyagi P;Motley SS;Koyama T;Kashyap M;Gingrich J;Yoshimura N;Fowke JH

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良性前列腺增生(BPH)与肥胖和前列腺组织炎症密切相关,但这种关系的分子基础尚不清楚。在此,我们研究了BPH患者尿液中趋化因子/脂肪因子水平与前列腺炎症、肥胖和下尿路症状LUTS的组织学标志物之间的关系。将入选纳什维尔男性健康研究的207例BPH/LUTS患者的冷冻尿液样本送去进行11种分析物的盲法分析,即sIL-1 RA、CXC趋化因子(CXCL-1、CXCL-8、CXCL-10)、CC趋化因子(CCL 2、CCL 3、CCL 5)、PDGF-BB、白细胞介素IL-6、IL-17和sCD 40 L,采用Luminex™ xMAP®技术。在调整年龄和药物使用后,使用线性回归将分析物的尿液水平与肥胖量表、前列腺炎症等级、程度和淋巴细胞浸润标志物(CD 3和CD 20)相关。经多重检验校正后,BPH患者的sIL-1 RA水平随着BMI、腰围和腰臀比的增加而显著升高(p=0.02)。具有更大的炎性浸润总体程度和最大CD 3浸润的男性分别与CXCL-10(p=0.054)和CCL 5(p=0.054)轻微相关。在15例中度至重度炎症患者中,CCL 3与最大CD 20浸润轻微相关(p=0.09),而在轻度前列腺组织炎症患者中检测不到CCL 3。sCD 40 L与AUA-SI评分存在边缘相关性(p=0.07)。尿中sIL-1 RA与较大体型的强相关性支持其作为BPH患者尿中肥胖的主要分子相关性。尿中CXCL-10、CCL 5和CCL 3水平的升高与前列腺组织炎症和淋巴细胞浸润评分轻微相关。总体而言,尿趋化因子升高支持BPH是一种代谢紊乱,并提示BPH/LUTS和前列腺炎症之间存在分子联系。
Benign prostatic hyperplasia (BPH) is strongly associated with obesity and prostatic tissue inflammation, but the molecular underpinning of this relationship is not known. Here, we examined the association between urine levels of chemokines/adipokines with histological markers of prostate inflammation, obesity and lower urinary tract symptoms LUTS in BPH patients. Frozen urine specimens from 207 BPH/LUTS patients enrolled in Nashville Men’s Health Study were sent for blinded analysis of 11 analytes, namely sIL-1RA, CXC chemokines (CXCL-1, CXCL-8, CXCL-10), CC chemokines (CCL2, CCL3, CCL5), PDGF-BB, interleukins IL-6, IL-17 and sCD40L using Luminex™ xMAP® technology. After adjusting for age and medication use, the urine levels of analytes were correlated with the scales of obesity, prostate inflammation grade, extent, and markers of lymphocytic infiltration (CD3 and CD20) using linear regression. sIL-1RA levels were significantly raised with higher BMI, waist circumference and waist-hip ratio in BPH patients after correction for multiple testing (p=0.02). Men with greater overall extent of inflammatory infiltrates and maximal CD3 infiltration were marginally associated with CXCL-10 (p=0.054) and CCL5 (p=0.054), respectively. CCL3 in 15 patients with moderate to severe grade inflammation was marginally associated with maximal CD20 infiltration (p=0.09), whereas CCL3 was undetectable in men with mild prostate tissue inflammation. There was marginal association of sCD40L with AUA-SI scores (p=0.07). Strong association of sIL-1RA in urine with greater body size supports it as a major molecular correlate of obesity in the urine of BPH patients. Increased urine levels of CXCL-10, CCL5 and CCL3 were marginally associated with the scores for prostate tissue inflammation and lymphocytic infiltration. Overall, elevated urinary chemokines support that BPH is a metabolic disorder and suggest a molecular link between BPH/LUTS and prostatic inflammation.
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发表时间: 2014-05
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影响因子: 2.8
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