Urinary extracellular vesicle-derived miR-126-3p predicts lymph node invasion in patients with high-risk prostate cancer.

To investigate extracellular vesicles (EVs), biomarkers for predicting lymph node invasion (LNI) in patients with high-risk prostate cancer (HRPCa), plasma, and/or urine samples were prospectively collected from 45 patients with prostate cancer (PCa) and five with benign prostatic hyperplasia (BPH). Small RNA sequencing was performed to identify miRNAs in the EVs. All patients with PCa underwent radical prostatectomy and extended pelvic lymph node dissection. Differentially expressed miRNAs were identified in patients with and without pathologically-verified LNI. The candidate miRNAs were validated in low-risk prostate cancer (LRPCa) and BPH. Four miRNA species (e.g., miR-126-3p) and three miRNA species (e.g., miR-27a-3p) were more abundant in urinary and plasma EVs, respectively, of patients with PCa. None of these miRNA species were shared between urinary and plasma EVs. miR-126-3p was significantly more abundant in patients with HR PCa with LNI than in those without (P = 0.018). miR-126-3p was significantly more abundant in the urinary EVs of patients with HRPCa than in those with LRPCa (P = 0.017) and BPH (P = 0.011). In conclusion, urinary EVs-derived miR-126-3p may serve as a good biomarker for predicting LNI in patients with HRPCa.

An effective urobilin clearance strategy based on paramagnetic beads facilitates microscale proteomic analysis of urine.

Urine provides an ideal source for disease biomarker discovery. High-adhesion contaminants such as urobilin, which are difficult to remove from urine, can severely interfere with urinary proteomic analysis. Here, we aimed to establish a strategy based on single-pot, solid-phase-enhanced sample preparation (SP3) technology to prepare samples for urinary proteomics analysis that almost completely eliminates the impact of urobilin. A systematic evaluation of the effects of two urinary protein precipitation methods, two types of protein lysis buffers, and different ratios of magnetic digestion beads on the identification and quantification of the microscale urinary proteome was conducted. Our results indicate that methanol-chloroform precipitation, coupled with efficient lysis facilitated by urea, and subsequent enzymatic digestion using a mix of hydrophilic and hydrophobic magnetic beads offers the best performance. Further applying this strategy to the urine of patients with benign prostatic hyperplasia, prostate cancer and healthy individuals, combined with a narrow window of data-independent acquisition, FGFR4, MYLK, ORM2, GOLM1, SPP1, CD55, CSF1, DLD and TIMP3 were identified as potential biomarkers to discriminate benign prostatic hyperplasia and prostate cancer patients.

Role of urine glycosaminoglycan levels in the diagnosis and follow-up in men with lower urinary tract symptoms.

OBJECTIVE: The aim of this study was to investigate whether urinary glycosaminoglycans (GAG) levels reflect clinical status in men with lower urinary tract symptoms and if they could be used as a marker in management of overactive bladder (OAB). METHODS: A total of 34 patients were recruited who were admitted with LUTS and diagnosed as having clinically bladder outlet obstruction (BOO) due to prostate enlargement. These newly diagnosed, never treated patients underwent routine investigation, consisting of history, physical examination, PSA, ultrasound, uroflowmetry, assessment of symptoms scored by both International Prostate Symptom Score (IPSS) and Marmara- Overactive Bladder Questionnaire (M-OBQ). The patients were divided into two groups as those with an initial M-OBQ score < 12 (group 1) and ≥ 13 (group 2). Alfa blocker was initiated in eligible patients. Further evaluations included prostate volume measurement, pre- and post-treatment urinary GAG levels, IPSS and M-QAOB values and maximum urine flow rate (Qmax). RESULTS: Before treatment, urinary GAG level was 21.5 mg/gCr (6.1-45.5) in Group 1, and 23.35 mg/gCr (15.6-32.6) in Group 2 (p =0.845). After the treatment, the GAG level in Group 1 and Group 2 were found to be 19.8 mg/gCr (7.4-70.5) and 18 (7.6- 41.7), respectively (p = 0.511). No difference in GAG levels was found in subgroup analysis for patients with or without OAB. CONCLUSIONS: In recent years, there have been many studies investigating the relationship between LUTS and urinary markers. However, in our prospective study, no relationship was found between pre- and post- treatment urinary GAG levels in patients with LUTS with or without OAB.

miRNA-21 as High Potential Prostate Cancer Biomarker in Prostate Cancer Patients in Indonesia.

OBJECTIVE: This study aimed to explore the diagnostic performance of miRNA-21 to differentiate between Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) patients in Indonesia. METHODS: Urine samples were collected from each PCa and BPH patient. miRNA-21 relative expression against the reference gene was analyzed and compared between the two. miRNA expression was then analyzed using the comparative quantification method to find the fold change. miR-21 validity in identifying PCa patients was performed by quantifying the sensitivity and specificity using samples in this study. RESULT: The results of this study indicated that miRNA-21 relative expression against miRNA-16 in PCa and BPH showed 12.95 differences in fold change. Moreover, using prostate biopsy as the gold standard to differentiate PCa and BPH, miRNA-21 Cq expression has 100% sensitivity and 75% specificity in differentiating the two. CONCLUSION: miRNA-21 relative expression can be used to discriminate PCa from BPH by using a urine sample. Furthermore, the expression of miR-21 has higher sensitivity than PSA; therefore, miR-21 has a high potential to be analyzed and developed further for clinical diagnosis of prostate cancer.

Identification of the metabolic signatures of prostate cancer by mass spectrometry-based plasma and urine metabolomics analysis.

OBJECTIVE: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men which is associated with profound metabolic changes. Systematic analysis of the metabolic alterations and identification of new biomarkers may benefit PCa diagnosis and a deep understanding of the pathological mechanism. The purpose of this study was to determine the metabolic features of PCa. METHODS: Plasma and urine metabolites from 89 prostate cancer (PCa) patients, 84 benign prostatic hyperplasia (BPH) patients, and 70 healthy males were analyzed using LC-MS/MS and GC-MS. The Orthogonalised Partial Least Squares Discriminant Analysis (OPLS-DA) was used to find the significantly changed metabolites. The clinical value of the candidate markers was examined by receiver operating characteristic curve analysis and compared with prostate-specific antigen (PSA). RESULTS: Multivariate statistical analyses found a series of altered metabolites, which related to the urea cycle, tricarboxylic acid cycle (TCA), fatty acid metabolism, and the glycine cleavage system. Plasma Glu/Gln showed the highest predictive value (AUC = 0.984) when differentiating PCa patients from healthy controls, with a higher sensitivity than PSA (96.6% vs. 94.4%). Both Glu/Gln and PSA displayed a low specificity when differentiating PCa patients from BPH patients (<53.2%), while the combination of Glu/Gln and PSA can further increase the diagnostic specificity to 66.9%. CONCLUSIONS: The present study showed the metabolic features of PCa, provided strong evidence that the amide nitrogen and the energy metabolic pathways could be a valuable source of markers for PCa. Several candidate markers identified in this study were clinically valuable for further assessment.

High level of phosphatidylcholines/lysophosphatidylcholine ratio in urine is associated with prostate cancer.

The altered levels of phospholipids (PLs) and lysophospholipids (LPLs) in prostate cancer (CaP) and benign tissues in our previous findings prompted us to explore PLs and LPLs as potential biomarkers for CaP. Urinary lipidomics has attracted increasing attention in clinical diagnostics and prognostics for CaP. In this study, 31 prostate tissues obtained from radical prostatectomy were assessed using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS). Urine samples were collected after digital rectal examination (DRE), and urinary lipids were extracted using the acidified Bligh-Dyer method. The discovery set comprised 75 patients with CaP and 44 with benign prostatic hyperplasia (BPH) at Kyoto University Hospital; the validation set comprised 74 patients with CaP and 59 with BPH at Osaka University Hospital. Urinary lipidomic screening was performed using MALDI time-of-flight MS (MALDI-TOF/MS). The levels of urinary lysophosphatidylcholine (LPC) and phosphatidylcholines (PCs) were compared between the CaP and BPH groups. The (PC [34:2] + PC [34:1])/LPC (16:0) ratio was significantly higher (P < .001) in CaP tissues than in benign epithelial tissues. The urinary PCs/LPC ratio was significantly higher (P < .001) in the CaP group than in the BPH group in the discovery and validation sets.

Urinary microRNA-1913 to microRNA-3659 expression ratio as a non-invasive diagnostic biomarker for prostate cancer.

PURPOSE: MicroRNAs (miRNAs) are small non-coding RNAs and are involved in the development, proliferation, and pathogenesis of prostate cancer (PCa). Urinary miRNAs are promising non-invasive biomarkers for PCa diagnosis because of their stability in urine. Here, we evaluated the diagnostic value of urinary miR-1913 to miR-3659 ratio in PCa patients and benign prostate hyperplasia (BPH) controls. MATERIALS AND METHODS: Candidate miRNAs were identified from urinary microarray data and tested by real-time PCR. The urinary miR-1913 to miR-3659 expression ratio was selected and tested in 83 urine samples (44 PCa and 39 BPH) to confirm its validity as a non-invasive diagnostic biomarker for PCa. RESULTS: The expression ratio of urinary miR-1913 to miR-3659 was significantly higher in PCa than in BPH (p=0.002) and showed a higher area under the receiver operating characteristic curve than prostate-specific antigen (PSA; 0.821 vs. 0.518) in patients within the PSA gray zone (tPSA: 3-10 ng/mL), with sensitivity of 75.0% and specificity of 78.6% (p=0.003). CONCLUSIONS: The urinary miR-1913 to miR-3659 expression ratio was increased in PCa and may serve as a useful supplemental biomarker to PSA for the diagnosis of PCa, particularly in patients within the PSA gray zone.

The Potential of hsa-mir-106b-5p as Liquid Biomarker in Prostate Cancer Patients in Indonesia.

PURPOSE: This study aims to explore the potential of hsa-mir-106b-5p as a new liquid biomarker for prostate cancer sufferers in Indonesia. METHODS: Analysis of hsa-mir-106b-5p expression of two tissue samples from BPH patients and two PCa patients used NanoString nCounter Expression Assay then validated by qRT-PCR using 10 patient urine samples for prostate cancer and BPH. Furthermore, analysis of the role of hsa-mir-106b-5p in prostate cancer was carried out bioinformatically. RESULTS: The results of this study indicated that the expression of hsa-mir-106b-5p in prostate cancer tissue was 1.23 times higher than that of BPH and urine of Indonesian patients (1.72 times). Moreover, this miRNA was upregulated in prostate cancer cells compared to normal cells 1.37 times. The hsa-mir-106b-5p appeared to be involved in the development of prostate cancer through the binding of genes involved in endoplasmic reticulum stress pathways and tumor suppressor genes. CONCLUSION: hsa-mir-106b-5p could modulate prostate cancer by interfering with the endoplasmic reticulum stress repair pathways and decreasing the expression of tumor suppressor genes involved in many biological processes. These updates our understanding of the role of hsa-mir-106b-5p in cancer and its potential as a candidate of a biomarker for clinical diagnosis of prostate cancer.

National trends in the use of PSA, urinalysis, and digital rectal exam for evaluation of lower urinary tract symptoms in men.

PURPOSE: The purpose of this study was to describe the practices of primary care physicians (PCPs) and urologists in their implementation of the 2010 American Urological Association (AUA) recommendations for the management of benign prostatic hyperplasia (BPH) in a nationally representative sample. METHODS: Data collected from 2008 to 2015 in the National Ambulatory Medical Care Survey (NAMCS) were used. Men aged 45 and older who presented with either a new complaint or exacerbation of lower urinary tract symptoms (LUTS) were included. Primary outcomes were the prevalence and determinants of prostate-specific antigen (PSA) testing, urinalysis (UA), and digital rectal exam (DRE), as all three were included in the AUA guidelines during the time period studied. In logistic regression analyses weighted to reflect national estimates, potential determinants of adherence for each testing modality were examined. RESULTS: Between 2008 and 2015, 878 visits met inclusion criteria, corresponding to 14,399,121 ambulatory visits for new or exacerbated LUTS. Weighted prevalence estimates were 24% for PSA testing (95% CI: 19-29%), 61% for urinalysis (95% CI: 56-66%), and 18% for DRE (95% CI: 15-23%). Age ≥ 75 years was associated with lower prevalence of testing for all three tests, and region was associated with different testing estimates for PSA and UA. Patients referred to urologists were more likely to receive a DRE, although overall rates of DRE decreased per additional year of data. CONCLUSIONS: Adherence to AUA guidelines for evaluation of LUTS in ambulatory visits was low in a nationally representative sample of Americans, particularly for PSA testing and DRE, suggesting substantial discordance between guidelines at the time and practice patterns. Practice patterns also differed by age and region. These discrepancies encourage increased education of providers in the implementation of the guidelines, particularly since they have been updated recently.

A novel urinary mRNA signature using the droplet digital polymerase chain reaction platform improves discrimination between prostate cancer and benign prostatic hyperplasia within the prostate-specific antigen gray zone.

Purpose: The aim of this study was to identify a noninvasive urinary marker for prostate cancer (PCa) diagnosis and to validate the clinical performance of this novel urinary mRNA signature using the droplet digital polymerase chain reaction (ddPCR) approach. Materials and Methods: A gene expression microarray (HT-12, Illumina Inc., USA) was used to identify genes differentially expressed between 16 PCa and 8 benign prostatic hyperplasia (BPH) tissues; ddPCR (QX200; Bio-Rad Laboratories, USA) was carried out to quantify the expression of selected genes in urine. The urinary molecular PCa risk score (UMPCaRS) was calculated by using the sum of three upregulated genes as the numerator and the sum of three downregulated genes as the denominator. The diagnostic utility of the UMPCaRS was validated by using a screening set (10 PCa and 10 BPH samples) and a validation set (131 PCa and 105 BPH samples). Results: Three upregulated genes (PDLIM5, GDF-15, THBS4) and three downregulated genes (UPK1A, SSTR3, NPFFR2) were selected from the microarray and subjected to ddPCR. The UMPCaRS for PCa in the screening and validation sets was significantly higher than that for BPH. For the validation set, the diagnostic accuracy of the UMPCaRS was comparable with that of prostate-specific antigen (PSA). Importantly, in the "PSA gray zone" (3-10 ng/mL), the AUC for the UMPCaRS was 0.843 and that for PSA was 0.628 (p<0.001). Conclusions: The data demonstrate that the UMPCaRS is useful for discriminating between PCa and BPH in the "PSA gray zone".

Urinary biomarkers of inflammation and tissue remodeling may predict bladder dysfunction in patients with benign prostatic hyperplasia.

PURPOSE: To evaluate the expression of urinary biomarkers of inflammation and tissue remodeling in patients with BPH undergoing surgery and evaluate the association of biomarkers with postoperative urodynamic outcomes MATERIALS AND METHODS: We analyzed urine samples from 71 patients treated with TURP from 2011 to 2017. Urinary levels of epidermal growth factor (EGF), matrix-metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), nerve growth factor (NGF) and monocyte-chemoattractant protein-1 (MCP-1) (by commercial ELISA kit) were measured, adjusted by urinary creatinine (Cr) and analyzed according to patients clinical and urodynamic characteristics (baseline and 12-month postoperative urodynamic) RESULTS: MMP-1/Cr levels were significantly higher among subjects with higher detrusor pressure on preoprative urodynamic. MCP-1/Cr levels were significantly higher amongs subjects with preoperative DO. Preoperative levels of NGF/Cr (0.13 vs 0.08, p = 0.005) and MMP-1/Cr (0.11 vs 0.04, p = 0.021) were predictors of persistent DO 12 months after surgery. The following factors were shown to be useful for predicting the persistence of DO in the postoperative period: NGF/Cr, with an AUC of 0.77 (95% CI 0.62-0.92) (p = 0.006), and MMP-1/Cr, with an AUC of 0.72 (95% CI 0.56-0.88) (p = 0.022). CONCLUSIONS: MMP-1/Cr was associated with higher detrusor pressure and MCP-1/CR with DO. NGF/Cr and MMP-1/Cr were shown to be predictors of persistent postoperative DO.

Body Mass Index and Risk of Prostate Volume, International Prostate Symptom Score, Maximum Urinary Flow Rate, and Post-Void Residual in Benign Prostatic Hyperplasia Patients.

The objective of this study was to evaluate association between body mass index (BMI) and prostate volume (PV), international prostate symptom scores (IPSS), maximum urinary flow rate (Qmax), and post-void residual (PVR) of Chinese benign prostatic hyperplasia (BPH) patients. All newly diagnosed BPH patients between September 2016 and August 2018 were selected and 788 patients were included. According to BMI, the patients were categorized into four groups, while according to PV, IPSS, Qmax, and PVR, they were categorized into two groups based on clinical significant cutoffs. Univariable and multivariable logistic regressions and a restricted cubic spline (RCS) were applied to explore the relationship of BMI with categorical PV, IPSS, Qmax, and PVR. Compared with normal BMI, obesity presented significant association with increased risk of larger PV (>80 ml) in both unadjusted and adjusted models (unadjusted odds ratio [OR] = 1.772, 95% CI [1.201, 2.614], p = .004; adjusted OR = 1.912, 95% CI [1.212, 3.017], p = .005); however, underweight or overweight did not present a significant connection with such risk. No significant effect was identified for BMI on IPSS, Qmax, or PVR in either unadjusted or adjusted model. Nonlinear test including BMI using RCS and adjusting for confounders showed no significance (p > .05); however, a significant linear relationship was ascertained between BMI and the risk of larger PV (p < .001). In conclusion, there was a significant linear association between BMI and the risk of larger PV in BPH patients. Hence, this suggests urologists should consider both BMI and PV when providing surgical treatment for BPH patients.

Data analysis algorithm for the development of extracellular miRNA-based diagnostic systems for prostate cancer.

Urine of prostate cancer (PCa) carries miRNAs originated from prostate cancer cells as a part of both nucleoprotein complexes and cell-secreted extracellular vesicles. The analysis of such miRNA-markers in urine can be a convenient option for PCa screening. The aims of this study were to reveal miRNA-markers of PCa in urine and design a robust and precise diagnostic test, based on miRNA expression analysis. The expression analysis of the 84 miRNAs in paired urine extracellular vesicles (EVs) and cell free urine supernatant samples from healthy donors, patients with benign and malignant prostate tumours was done using miRCURY LNA miRNA qPCR Panels (Exiqon, Denmark). Sets of miRNAs differentially expressed between the donor groups were found in urine EVs and urine supernatant. Diagnostically significant miRNAs were selected and algorithm of data analysis, based on expression data on 24-miRNA in urine and obtained using 17 analytical systems, was designed. The developed algorithm of data analysis describes a series of steps necessary to define cut-off values and sequentially analyze miRNA expression data according to the cut-offs to facilitate classification of subjects in case/control groups and allows to detect PCa patients with 97.5% accuracy.

Sex hormones and oxidative stress mediated phthalate-induced effects in prostatic enlargement.

Prostatic enlargement might affect up to 30% of men and can cause signs and symptoms in the lower urinary tract in the elderly. Imbalanced estrogen and androgen secretions are important in prostatic physiopathology. Phthalates-environmental endocrine disruptors-affect androgen secretion and disrupt sexual organs, including testes and the prostate, but the underlying mechanisms are unclear. Using European Association of Urology (EAU) guidelines, we recruited from urology clinics in southern Taiwan 207 elderly men diagnosed with benign prostatic hyperplasia (BPH) and prostatic enlargement between 2015 and 2017. We took blood and urine samples from all patients on the same day. We used multivariate linear regression, associations, and potential interactions after we had measured and analyzed oxidative stress (OS) markers, steroidal hormones, and 11 urinary phthalate metabolites, and then we adjusted for confounders. Di(2-ethylhexyl) phthalate (DEHP) metabolite levels, particularly urinary mono-(2-ethylhexyl) phthalate, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), prostate specific antigen (PSA), and prostate volume (PV) (p < 0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and OS markers (p < 0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E2), the converted enzymes aromatase and 5α reductase, and reactive oxygen species (ROS) (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.

Screening, identification of prostate cancer urinary biomarkers and verification of important spots.

Prostate-specific antigen (PSA) has been widely used as the unique serum biomarker for the diagnosis of prostate cancer (PCa). When PSA is moderately increased (e.g., 4-10 ng/ml), it is difficult to differentiate benign prostatic hyperplasia (BPH) from cancer. The diagnostic test (i.e., prostate biopsy) is invasive, adding pain and economic burden to the patient. Urine samples are more convenient, non-invasive and readily available than blood. We sought to determine whether ferritin might be the potential urinary biomarker in prostate cancer diagnosis. Using two-dimensional electrophoresis (2DE) followed by mass spectrometry (MS), differentially expressed urinary proteins among patients with PCa, BPH and normal controls were obtained. The ferritin heavy chain (FTH) gene, ferritin light chain (FTL) gene and protein expression of BPH-1 cells and PC-3 cells were analyzed by real-time quantitative PCR and Western blotting, respectively. Stable FTH or FTL silenced cell lines were generated by small hairpin(sh) RNA lentiviral transfection. The function of the cell lines was evaluated by the colony formation assay, transwell assay, and flow cytometry. Compared with BPH and normal controls, 15 overexpressed proteins, including FTH and FTL, were identified in the urine of the PCa group. FTH and FTL were also highly expressed in PC-3 cell lines compared with BPH-1 cells. FTH-silenced cells showed reduced cell proliferation, migration and increased cell apoptosis. FTL-silenced cells showed increased proliferation and migration abilities. There are differences in urinary proteins among patients with PCa, BPH and normal controls. FTH and FTL play different roles in PCa cells and are potential biomarkers for PCa.

Colorimetric detection of PCA3 in urine for prostate cancer diagnosis using thiol-labeled PCR primer and unmodified gold nanoparticles.

BACKGROUND: PCA3, a non-coding RNA, has been approved as a potential urinary biomarker for prostate cancer. However, PCA3 urine tests have some limitations. Therefore, we developed a colorimetric method for PCA3 detection in urine. METHODS: The assay was based on interactions between unmodified gold nanoparticles (AuNPs) and thiolated PCR products. Thiolated PCR products were amplified by RT-PCR using a thiol-labeled primer at the 5' end. Thiolated products of PCA3 bound to the surface of AuNPs and led to the prevention of salt-induced aggregation (red color). In the absence of the PCR products, AuNPs changed their color from red to blue due to the salt-induced aggregation. These changes were detected by the naked eye and spectrophotometer. RESULTS: Our assay was specific for PCA3 in prostate cancer cell lines with a visual detection limit of 31.25 ng/reaction. The absorption ratio 520/640 nm was linear against PCR product concentration (R2 = 0.9798) in the reaction. This method is promising for discrimination of prostate cancer patients from both healthy controls and benign prostatic hyperplasia patients according to their urinary PCA3 expression levels. CONCLUSIONS: This study established a simple, rapid, sensitive and specific assay for PCA3 detection which may be applicable for prostate cancer diagnosis.

Post-treatment urinary sarcosine as a predictor of recurrent relapses in patients with prostate cancer.

To date, there has been no evidence regarding the association between urinary sarcosine content and prostate cancer survival. Our main objective was to investigate whether levels of post-treatment urinary sarcosine are associated with relapse. The inclusion criteria were (in accordance with EAU 2017) as follows: histopathologically verified adenocarcinoma in prostate biopsy cores or specimens from transurethral resection of the prostate (TURP) or prostatectomy for benign prostatic enlargement (BPE) with retained ability to urinate. The median follow-up was 53 months. In the study, we retrospectively evaluated a cohort of 511 patients with prostate cancer with various risk factors and treatment strategies. Post-treatment sarcosine levels were elevated in 266 (52%) patients and highly elevated (≥200 nmol/L) in 71 (13%) patients. Urinary sarcosine content was significantly associated with number of relapses that patients experienced, P = 0.002 for sarcosine ≥200 vs ≤30 nmol/L. Multivariate analysis revealed that sarcosine was an independent predictor of recurrent relapses (≥2 relapses with an intermediate period of remission), HR = 3.89 (95% CI 1.29-11.7) for sarcosine >200 vs <30 nmol/L. This trend was even more pronounced in a subgroup of patients who underwent radical prostatectomy, HR = 3.29 (95% CI 1.06-10.18), where (single) relapse-free survival could also be predicted by sarcosine levels, HR = 1.96 (1.05-3.66). Urinary sarcosine may become a possible predictor for patients' outcomes, because patients with elevated post-treatment sarcosine could be predicted to have recurrent relapses of the disease.

Change of the 5α/5ß ratio of urinary steroid metabolites in benign prostatic hyperplasia patients treated with dutasteride.

BACKGROUND: The effects of the administration of dutasteride (DUT) on steroid metabolite pathways in BPH patients have not been examined. METHODS: Urine and blood samples as well as clinical parameters were prospectively collected after the administration of DUT to 60 BPH patients, and after its withdrawal in another set of 25 BPH patients. Urine samples were assessed using gas chromatography/mass spectrometry for the urinary steroid profile (USP), which simultaneously measures 63 steroid metabolites. We examined pharmacological changes in the 5α/5ß ratio of urinary metabolites and their relationships with clinical parameters in patients treated with DUT. RESULTS: The mean urinary androsterone/etiocholanolone (An/Et) ratio in sex-steroid pathways significantly decreased from 1.39 to 0.02 (p < 0.01). Urinary metabolites in other steroid pathways such as 5αTHF/5ßTHF in the glucocorticoid pathway and 5αTHB/5ßTHB in the mineralocorticoid pathway also significant decreased after the DUT treatment. As compared to baseline level, the mean An/Et ratios in patients with the withdrawal of DUT were 0.7%, 1.4%, 12.6%, and 82.4% at just before, one month, 3 months, and 6 months after the withdrawal of DUT, respectively. All other steroid pathways changed in a similar manner without the aggravation of urinary symptoms. The recovery ratio of An/Et in USP before and 3 months after the withdrawal of DUT correlated with the recovery ratio of serum PSA levels (ρ = 0.61, p < 0.01). CONCLUSION: Urinary 5α/5ß metabolites in all pathways were strongly suppressed after the administration of DUT for one month and the pharmacological effect of DUT prolonged even after withdrawal of DUT.

Two long non-coding RNAs, Prcat17.3 and Prcat38, could efficiently discriminate benign prostate hyperplasia from prostate cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) have recently appeared as new players in cancer biology. Recently, a number of new prostate cancer-associated lncRNAs has been listed via RNA-seq approach by Mitranscriptome project. By analyzing this data we chose four lncRNAs (Prcat17.3, Prcat38, Prcat47, and Cat2184.4) and evaluated their expressions and their abilities to discriminate prostate tumors from benign prostate hyperplasia (BPH). METHODS: Fresh Prostate tissue samples (30 BPH, and 30 tumor samples) and urine samples (19 BPH, and 19 tumor samples) were collected and their total RNA extracted for cDNA syntheses. The expression of candidate lncRNAs was assessed by the real-time PCR technique. RESULTS: Our data revealed that the expression levels of PRCAT17.3 (P < 0.0001) and PRCAT38 (P < 0.0002) were significantly upregulated in human prostate cancer tissues, compared to BPH ones. Moreover, the altered expression was much higher for PRCAT17.3 (∼2000 folds) than PRCAT38 (∼50 folds). In contrast, the expression of Cat2184.4 showed a significant down-regulation in tumor samples (P < 0.0001), compared to BPH ones. While the expression level of PRCAT47 was increased in cancer samples, the changes were not statistically significant. In discriminating prostate tumors from BPH samples, Prcat17.3 (AUC-ROC, 0.927) demonstrated a better diagnostic efficacy than Prcat38 (AUC-ROC, 0.778). Moreover, real-time RT-PCR analyses on urine samples of prostate cancer patients revealed that prcat17.3 level is significantly elevated, (P < 0.0197; AUC-ROC value of 0.72), compared to that of BPH patients. CONCLUSION: We introduce here two novel lncRNAs with a potential application in diagnosis of prostate cancer.

Efficacy and safety of a hexanic extract of Serenoa repens (Permixon® ) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis of randomised controlled trials and observational studies.

OBJECTIVES: To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon® ; Pierre Fabre Médicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge (Institute for Scientific Information), Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data were collected on International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax ), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADRs). Data obtained from RCTs and observational studies were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies that included patients on longer-term treatment (≥1 year). RESULTS: Data from 27 studies (15 RCTs and 12 observational studies) were included for meta-analysis (total N = 5 800). Compared with placebo, the HESr was associated with 0.64 (95% confidence interval [CI] -0.98 to -0.31) fewer voids/night (P < 0.001) and an additional mean increase in Qmax of 2.75 mL/s (95% CI 0.57 to 4.93; P = 0.01). When compared with α-blockers, the HESr showed similar improvements on IPSS (weighted mean difference [WMD] 0.57, 95% CI -0.27 to 1.42; P = 0.18) and a comparable increase in Qmax to tamsulosin (WMD -0.02, 95% CI -0.71 to 0.66; P = 0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5α-reductase inhibitors (5ARIs). Analysis of all available published data for the HESr showed a mean improvement in IPSS from baseline of -5.73 points (95% CI -6.91 to -4.54; P < 0.001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on prostate-specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for ≥1 year (n = 447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%). CONCLUSION: The present meta-analysis, which includes all available RCTs and observational studies, shows that the HESr (Permixon) reduced nocturia and improved Qmax compared with placebo and had a similar efficacy to tamsulosin and short-term 5-ARI in relieving LUTS. HESr (Permixon) appears to be an efficacious and well-tolerated therapeutic option for the long-term medical treatment of LUTS/BPH.