Abstract. Monocyte chemotactic protein-1 (MCP-1) is differentially expressed in benign prostatic hyperplasia (BPH) and is a potential clinical biomarker for BPH. We collected urine post-digital rectal examination (DRE) from 48 men who did not have a diagnosis of prostate cancer. We measured MCP-1 levels by enzyme-linked immunosorbent assay (ELISA) and compared them with prostate weight and lower urinary tract symptoms (LUTS) as measured by the International Prostate Symptom Score (I-PSS) utilizing correlation and regression analyses. In post-DRE urine, higher MCP-1 levels were associated with increased I-PSS but not with prostate volume. MCP-1 levels in men with prostate enlargement were significantly higher than those in men without enlargement. In multivariable regression adjusting for age, prostate volume, and PSA,higher urinary MCP-1 was associated with significantly higher I-PSS. Since MCP-1 is preferentially expressed in BPH tissue, these data suggest that MCP-1 may be a novel biomarker for clinically significant BPH.Keywords: MCP-1, LUTS, urine marker, benign prostatic hyperplasia IntroductionBenign prostate hyperplasia (BPH) is a common disease affecting older men caused by unregulated prostatic stromal and epithelial growth resulting in prostate enlargement, bladder outlet obstruction, and lower urinary tract symptoms (LUTS) [1]. Despite intensive researches over the last several decades, the molecular mechanisms underlying prostatic enlargement and symptomatic bladder outlet obstruction remain obscure, and specific clinical markers for symptomatic BPH have yet to be developed. We previously used a human cytokine array to search for cytokines in expressed prostatic secretions (EPS) from radical prostatectomy specimens that may be associated with prostate enlargement, and found that monocyte/macrophage chemoattractant protein-1 (MCP-1, CCL2) in EPS was associated with prostate size [2]. MCP-1 is a member of the CC chemokine superfamily and plays a critical role in the recruitment and activation of monocytes during inflammation [3]. MCP-1 is secreted from prostatic stromal cells and stimulates the proliferation of prostatic epithelial cells in vitro. Immunohistochemical studies indicated that MCP-1 was upregulated in benign prostatic hyperplasia (BPH) lesions, and MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 [4]. Based on these data, we hypothesize that MCP-1 levels in urine after DRE, which is enriched in prostatic contents, could serve as a specific clinical marker for symptomatic BPH. Therefore, we evaluated associations of MCP-1 levels in urine collected after DRE with prostate volume and LUTS by enzyme-linked immunosorbent assay (ELISA).
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