Dysregulation of the miRNome unveils a crosstalk between obesity and prostate cancer: miR-107 asa personalized diagnostic and therapeutic tool.

Prostate-specific antigen (PSA) is the gold-standard marker to screen prostate cancer (PCa) nowadays. Unfortunately, its lack of specificity and sensitivity makes the identification of novel tools to diagnose PCa an urgent medical need. In this context, microRNAs (miRNAs) have emerged as potential sources of non-invasive diagnostic biomarkers in several pathologies. Therefore, this study was aimed at assessing for the first time the dysregulation of the whole plasma miRNome in PCa patients and its putative implication in PCa from a personalized perspective (i.e., obesity condition). Plasma miRNome from a discovery cohort (18 controls and 19 PCa patients) was determined using an Affymetrix-miRNA array, showing that the expression of 104 miRNAs was significantly altered, wherein six exhibited a significant receiver operating characteristic (ROC) curve to distinguish between control and PCa patients (area under the curve [AUC] = 1). Then, a systematic validation using an independent cohort (135 controls and 160 PCa patients) demonstrated that miR-107 was the most profoundly altered miRNA in PCa (AUC = 0.75). Moreover, miR-107 levels significantly outperformed the ability of PSA to distinguish between control and PCa patients and correlated with relevant clinical parameters (i.e., PSA). These differences were more pronounced when considering only obese patients (BMI > 30). Interestingly, miR-107 levels were reduced in PCa tissues versus non-tumor tissues (n = 84) and in PCa cell lines versus non-tumor cells. In vitro miR-107 overexpression altered key aggressiveness features in PCa cells (i.e., proliferation, migration, and tumorospheres formation) and modulated the expression of important genes involved in PCa pathophysiology (i.e., lipid metabolism [i.e., FASN] and splicing process). Altogether, miR-107 might represent a novel and useful personalized diagnostic and prognostic biomarker and a potential therapeutic tool in PCa, especially in obese patients.

In1-Ghrelin Splicing Variant as a Key Element in the Pathophysiological Association Between Obesity and Prostate Cancer.

CONTEXT: Recent studies emphasize the importance of considering the metabolic status to develop personalized medicine approaches. This is especially relevant in prostate cancer (PCa), wherein the diagnostic capability of prostate-specific antigen (PSA) dramatically drops when considering patients with PSA levels ranging from 3 to 10 ng/mL, the so-called grey zone. Hence, additional noninvasive diagnostic and/or prognostic PCa biomarkers are urgently needed, especially in the metabolic-status context. OBJECTIVE: To assess the potential relation of urine In1-ghrelin (a ghrelin-splicing variant) levels with metabolic-related/pathological conditions (eg, obesity, diabetes, body mass index, insulin and glucose levels) and to define its potential clinical value in PCa (diagnostic/prognostic capacity) and relationship with PCa risk in patients with PSA in the grey zone. METHODS: Urine In1-ghrelin levels were measured by radioimmunoassay in a clinically, metabolically, pathologically well-characterized cohort of patients without (n = 397) and with (n = 213) PCa with PSA in the grey zone. RESULTS: Key obesity-related factors associated with PCa risk (BMI, diabetes, glucose and insulin levels) were strongly correlated to In1-ghrelin levels. Importantly, In1-ghrelin levels were higher in PCa patients compared to control patients with suspect of PCa but negative biopsy). Moreover, high In1-ghrelin levels were associated with increased PCa risk and linked to PCa aggressiveness (eg, tumor stage, lymphovascular invasion). In1-ghrelin levels added significant diagnostic value to a clinical model consisting of age, suspicious digital rectal exam, previous biopsy, and PSA levels. Furthermore, a multivariate model consisting of clinical and metabolic variables, including In1-ghrelin levels, showed high specificity and sensitivity to diagnose PCa (area under the receiver operating characteristic curve = 0.740). CONCLUSIONS: Urine In1-ghrelin levels are associated with obesity-related factors and PCa risk and aggressiveness and could represent a novel and valuable noninvasive PCa biomarker, as well as a potential link in the pathophysiological relationship between obesity and PCa.

The protective role of coenzyme Q10 in renal injury associated with extracorporeal shockwave lithotripsy: a randomised, placebo-controlled clinical trial.

OBJECTIVE: To determine the efficacy of coenzyme Q10 (CoQ10) in preventing renal injury in patients with lithiasis undergoing extracorporeal shockwave lithotripsy (ESWL). PATIENTS AND METHODS: Prospective, randomised, double-blind, placebo-controlled clinical trial of 100 patients with renal lithiasis who were treated with ESWL. The patients were distributed randomly into two groups receiving either placebo or CoQ10 (200 mg/day), a powerful antioxidant with vasoactive properties, orally administered during the week before ESWL and for 1 week after. Renal dysfunction markers, vasoactive hormones, oxidative stress, plasma levels of several interleukins and vascular resistance index (VRI) using Doppler ultrasound were evaluated the week before ESWL, 2 h before ESWL and at 2 h, 24 h and 7 days after ESWL. RESULTS: There was a significant increase in glomerular filtration (P = 0.013), as well as a decrease in the albumin/creatinine ratio and the ß2 -microglobulin level (P = 0.02) after 1 week of treatment in the CoQ10 group. These changes were maintained at the follow-up after ESWL. The administration of CoQ10 was associated with improvement in vasoactive hormone parameters, VRI and interleukin levels. These improvements were maintained until the end of the follow-up period. However, the administration of CoQ10 was not associated with significant changes in the oxidative stress parameters. CONCLUSION: Our results indicate that CoQ10 administration improves renal function and vasoactive and inflammation parameter values, allowing for preconditioning before the tissue insult caused by ESWL.