Cochetti Giovanni, Poli Giulia, Guelfi Gabriella, Boni Andrea, Egidi Maria Giulia, Mearini Ettore
Department of Surgical and Biomedical Sciences, Institution of Urological, Andrological Surgery and Minimally Invasive Techniques.
Department of Experimental Medicine, Section of Terni.
Onco Targets Ther. 2016 Dec 13;9:7545-7553. doi: 10.2147/OTT.S119027. eCollection 2016.
Diagnosis of prostate cancer (PCa) is based on prostate biopsy that is performed when prostate specific antigen (PSA) is persistently altered over time and/or abnormal digital rectal examination is found. Serum PSA levels increase in both PCa and benign prostatic hyperplasia, leading to an increased number of unnecessary biopsies. There is an urgent need to unravel PCa-specific molecular signatures.
This study aimed at characterizing a panel of circulating micro RNAs (miRNAs) that could distinguish PCa from benign prostatic hyperplasia in a population of age-matched patients with increased PSA levels. Both miRNAs targeting genes involved in PCa onset and miRNAs whose role in PCa has been highlighted in other studies were included. For this purpose, let-7c, let-7e, let-7i, miR-26a-5p, miR-26b-5p, miR-24-3p, miR-23b-3p, miR-27-b-3p, miR-106a-5p, miR-20b-5p, miR-18b-5p, miR-19b-2-5p, miR-363-3p, miR-497, miR-195, miR-25-3p, miR-30c-5p, miR-622, miR-874-3p, miR-346 and miR-940 were assayed through real-time PCR in 64 patients with PCa and compared with 60 patients with benign prostatic hyperplasia. The ability of miRNAs to predict the stage of disease was also analyzed.
Let-7c, let-7e, let-7i, miR-26a-5p, miR-26b-5p, miR-18b-5p and miR-25-3p were able to discriminate patients with PCa from those harboring benign prostatic hyperplasia, both presenting altered PSA levels (>3 ng/mL). MiR-25-3p and miR-18b-5p showed the highest sensitivity and specificity to predict PCa, respectively. The combination of these two miRNAs improved the overall sensitivity. A correlation between pathological Gleason score and miRNA expression levels was reported; miR-363-3p, miR-26a-5p, miR-26b-5p, miR-106a-5p, miR-18b-5p, miR-25-3p and let-7i decreased in expression concomitantly with an increase in malignancy.
This study confirms serum miRNAs to be reliable candidates for the development of minimally invasive biomarkers for the diagnosis and prognosis of PCa, particularly in those cases where PSA acts as a flawed marker.
前列腺癌（PCa）的诊断基于前列腺活检，通常在前列腺特异性抗原（PSA）随时间持续变化和/或直肠指检异常时进行。PCa和良性前列腺增生时血清PSA水平均会升高，导致不必要活检的数量增加。迫切需要揭示PCa特异性分子特征。
本研究旨在鉴定一组循环微小RNA（miRNA），以在PSA水平升高的年龄匹配患者群体中区分PCa和良性前列腺增生。纳入了靶向参与PCa发生相关基因的miRNA以及在其他研究中已突显其在PCa中作用的miRNA。为此，通过实时PCR检测了64例PCa患者和60例良性前列腺增生患者中的let-7c、let-7e、let-7i、miR-26a-5p、miR-26b-5p、miR-24-3p、miR-23b-3p、miR-27-b-3p、miR-106a-5p、miR-20b-5p、miR-18b-5p、miR-19b-2-5p、miR-363-3p、miR-497、miR-195、miR-25-3p、miR-30c-5p、miR-622、miR-874-3p、miR-346和miR-940，并进行比较。还分析了miRNA预测疾病分期的能力。
Let-7c、let-7e、let-7i、miR-26a-5p、miR-26b-5p、miR-18b-5p和miR-25-3p能够区分PSA水平改变（>3 ng/mL）的PCa患者和良性前列腺增生患者。MiR-25-3p和miR-18b-5p分别显示出预测PCa的最高敏感性和特异性。这两种miRNA的组合提高了总体敏感性。报道了病理Gleason评分与miRNA表达水平之间的相关性；miR-363-3p、miR-26a-5p、miR-26b-5p、miR-106a-5p、miR-18b-5p、miR-25-3p和let-7i的表达随恶性程度增加而降低。
本研究证实血清miRNA是开发用于PCa诊断和预后的微创生物标志物的可靠候选物，特别是在PSA作为有缺陷标志物的情况下。
