Detection of circulating miRNAs as possible biomarkers of prostate cancer associated to metabolic syndrome.

DALTON GN; PICCIONI F; DE SIERVI A; MASSILLO C; DE LUCA P; MASSILLO C; DE LUCA P; FARRÉ PL; SCALISE G; FARRÉ PL; SCALISE G; DALTON GN; PICCIONI F; DE SIERVI A

Mar del Plata

Congreso; LXIII Reunión Annual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Prostate cancer (PCa) is the most common type of cancer and is thethird cause of death by cancer among males in Argentina. Metabolicsyndrome (MeS) is a cluster of pathophysiological disorders whosediagnose requires the detection of, at least, three of the followingfactors: visceral adiposity, high triglycerides, low High Density Lipoprotein(HDL) cholesterol levels, high blood pressure and elevatedfasting glucose levels. A recent meta-analysis found a significantcorrelation associating MeS with more aggressive PCa tumorsand biochemical recurrence. C-terminal binding protein (CTBP1)is a transcriptional co-repressor of many tumor suppressor genes.Binding either NAD+ or NADH is necessary for CTBP1 activation;however, CTBP1 affinity is 100-fold higher for NADH making it amolecular sensor of the metabolic state of the cell and an interestinglink between PCa and MeS. Recent years have seen an overflow ofreports regarding miRNAs role in cancer. Many reviews have beenpublished on miRNAs deregulation in cancer, both as cause andconsequence, and as possible biomarkers or therapeutic molecules.In this work our aim was the identification of circulating miRNAs tobe used in the near future as biomarkers of PCa associated to MeS.To this end, we analyzed serum samples collected from mice bearingxenotransplants and detected 4 miRNAs by RT-qPCR. Amongthem miR-30b-5p was significantly down regulated in the circulationof MeS mice that were inoculated with control CTBP1 expressioncells compared to the mice inoculated with CTBP1 depleted cells.We also analyzed circulating miRNA levels on PCa patient serumsamples that were clustered depending on Gleason Score and parametersassociated to MeS. In addition, we analyzed serum samplesfrom benign prostatic hyperplasia (BPH) patients and healthydonors, which were clustered according to MeS parameters. We identified many candidates for further analysis as possible biomarkers of PCa associated to MeS.