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

Pradeep Tyagi, Saundra S. Motley, Tatsuki Koyama, Mahendra Kashyap, Jeffrey Gingrich, Naoki Yoshimura, Jay Fowke

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalProstate
Volume78
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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Prostatic Hyperplasia
Obesity
Urine
Inflammation
Prostate
Chemokines
Interleukin-6
Chemokine CCL3
Men's Health
CXC Chemokines
CC Chemokines
Lower Urinary Tract Symptoms
Adipokines
Waist-Hip Ratio
Interleukin-17
Chemokine CCL2
Body Size
Waist Circumference
Linear Models
Technology

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Cite this

Tyagi, P., Motley, S. S., Koyama, T., Kashyap, M., Gingrich, J., Yoshimura, N., & Fowke, J. (2018). Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients. Prostate, 78(1), 17-24. https://doi.org/10.1002/pros.23439

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients. / Tyagi, Pradeep; Motley, Saundra S.; Koyama, Tatsuki; Kashyap, Mahendra; Gingrich, Jeffrey; Yoshimura, Naoki; Fowke, Jay.

In: Prostate, Vol. 78, No. 1, 01.01.2018, p. 17-24.

Research output: Contribution to journalArticle

Tyagi, P, Motley, SS, Koyama, T, Kashyap, M, Gingrich, J, Yoshimura, N & Fowke, J 2018, 'Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients', Prostate, vol. 78, no. 1, pp. 17-24. https://doi.org/10.1002/pros.23439
Tyagi P, Motley SS, Koyama T, Kashyap M, Gingrich J, Yoshimura N et al. Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients. Prostate. 2018 Jan 1;78(1):17-24. https://doi.org/10.1002/pros.23439
Tyagi, Pradeep ; Motley, Saundra S. ; Koyama, Tatsuki ; Kashyap, Mahendra ; Gingrich, Jeffrey ; Yoshimura, Naoki ; Fowke, Jay. / Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients. In: Prostate. 2018 ; Vol. 78, No. 1. pp. 17-24.
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abstract = "Purpose: 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. Methods: 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{\circledR} 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. Results: 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). Conclusions: 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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T1 - Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

AU - Tyagi, Pradeep

AU - Motley, Saundra S.

AU - Koyama, Tatsuki

AU - Kashyap, Mahendra

AU - Gingrich, Jeffrey

AU - Yoshimura, Naoki

AU - Fowke, Jay

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N2 - Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.

AB - Purpose: 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. Methods: 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. Results: 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). Conclusions: 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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