Download a new potential biomarker for prostate cancer diagnosis

PLASMA CIRCULATING MIRNAS: A NEW POTENTIAL BIOMARKER FOR
PROSTATE CANCER DIAGNOSIS
S. Giglio, C. De Nunzio, R. Cirombella, F. Esperto, F. Presicce, A. Tubaro, A. Vecchione
(Roma)
Aim of the study
Recent studies have demonstrated that aberrant expressions of miRNAs are closely associated
with the development, invasion, metastasis and prognosis of various cancers including prostate
cancer. Circulating miRNAs may be useful for early diagnosis as well as to predict the clinical
outcome and the treatment response. The aim of this study was to investigate the hypothesis that
changes in circulating miRNAs represent potentially useful biomarkers for the diagnosis of
prostate cancer.
Materials and methods
From 2013 onwards, a consecutive men undergoing 12-core prostate biopsy at one center in Italy
were enrolled into a prospective database. Indications for a prostatic biopsy were a PSA value ≥
4 ng/ml and/or a positive digital rectal examination (DRE). 7,5 ml EDTA blood sample were
drawn before the biopsy, the samples were centrifuged at 1800 RPM for 20 min and the plasma
stored at -20°C. Total RNAs has been extracted using Plasma/serum Circulating and Exosomal
RNA purification mini kit (NorgenBiotek) and assessed on RNA 6000 Nano Chip using an
Agilent 2100 bioanalyzer (Agilent Technologies). Next generation sequencing (NGS) have been
carried out at the Department of Molecular Virology, Immunology and Medical Genetics and
Comprehensive Cancer Center, Ohio State University, OH, USA using SOLiD5500XL (Applied
Biosystems). Receiver-operator characteristics (ROC) curve analysis was used to evaluate the
diagnostic accuracy of miRNAs for the final histopathological diagnosis of prostate cancer.
Results
32 patients were enrolled with a mean age and PSA of 66.6 years (SD ±7.9) and 14.3 (range to
0,53-185) ng/ml, respectively. 16 patients (50%) had cancer on biopsy; 8 with Gleason score 6; 3
with a Gleason score 7 and 5 with a Gleason score ≥8. Profiling of microRNAs by deep
sequencing allowed to identify a "signature" of 27microRNAs aberrant expressed in prostate
cancer samples. 24miRNAs were over-expressed and 3 were down-regulated in patients with
prostate cancer when compared to patients with a negative biopsy. Specifically, ROC curve
analysis also showed as a small subgroup consisting of 6 miRNAs (miR-125b, miR-532-5p,
miR-874, miR-3940, miR-188-5p, miR-15a*) presented a good performance to discriminate
patients with prostate cancer (AUC = 0.805; 95%CI; 0.77-0.85).
Discussion
NGS seems to be a valid method to evaluate miRNAoma. In our experience mRNA presented a
good accuracy for the detection of PCa.
Conclusions
Our preliminary results, although should be validated in a large group of patients that is ongoing
in our centre, confirmed the possible role of miRNA as novel biomarker for the diagnose of
patients with prostate cancer.