Stuopelytė Kristina, Daniūnaitė Kristina, Jankevičius Feliksas, Jarmalaitė Sonata
Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
Urology Centre, Vilnius University, Vilnius, Lithuania; National Cancer Institute, Vilnius, Lithuania.
Medicina (Kaunas). 2016;52(2):116-24. doi: 10.1016/j.medici.2016.02.007. Epub 2016 Mar 11.
Prostate cancer (PCa) is the second most prevalent oncologic disease among men worldwide. Expression of various transcripts, including miRNAs, is markedly deregulated in cancerous prostate tissue. This study aimed at identifying a PCa-specific expression profile of miRNAs for subsequent use in noninvasive diagnostics.
MiRNA expression was profiled in 13 PCa tissues using human miRNA microarrays. Highly expressed miRNAs were selected for the analysis in urine of patients with PCa (N=143) and benign prostate hyperplasia (BPH; N=23) by means of real time PCR, while miRNAs showing the expression differences in relation to clinical variables were further analyzed in 52 PCa and 12 noncancerous prostate tissues (NPT) on TaqMan Low Density Arrays (TLDA).
Analysis of miRNA expression in prostate tissue linked miR-95 to aggressive form of PCa. This miRNA was up-regulated in high grade (P=0.041), the TMPRSS2-ERG fusion-positive tumors (P=0.026), and in patients with subsequently developed biochemical recurrence (BCR; P=0.054) after radical prostatectomy. MiRNAs highly expressed in PCa tissues were also detectable in urine from PCa patients. Moreover, the urinary levels of miR-21 had significant discriminatory power (P=0.010) to separate PCa patients from BPH, while the combined analysis of urinary miR-19a and miR-19b was prognostic for BCR. In PCa, the diagnostic potential of urinary miRNA panel (miR-21, miR-19a, and miR-19b) was higher than that of the PSA test (AUC=0.738 vs. AUC=0.514).
Measurement of urinary levels of PCa-specific miRNAs could assist in more specific detection of PCa and prediction of BCR.
前列腺癌（PCa）是全球男性中第二常见的肿瘤性疾病。包括微小RNA（miRNA）在内的各种转录本的表达在癌性前列腺组织中明显失调。本研究旨在鉴定PCa特异性的miRNA表达谱，以供后续用于无创诊断。
使用人类miRNA微阵列对13例PCa组织中的miRNA表达进行分析。通过实时聚合酶链反应（PCR），选择高表达的miRNA对PCa患者（N = 143）和良性前列腺增生（BPH；N = 23）患者的尿液进行分析，而在TaqMan低密度阵列（TLDA）上，对52例PCa组织和12例非癌性前列腺组织（NPT）中与临床变量相关的表达存在差异的miRNA进行进一步分析。
对前列腺组织中miRNA表达的分析将miR-95与侵袭性PCa形式联系起来。该miRNA在高级别（P = 0.041）、TMPRSS2-ERG融合阳性肿瘤（P = 0.026）以及前列腺癌根治术后随后发生生化复发（BCR；P = 0.054）的患者中上调。在PCa组织中高表达的miRNA在PCa患者的尿液中也可检测到。此外，miR-21的尿液水平具有显著的鉴别能力（P = 0.010），可将PCa患者与BPH患者区分开来，而尿液miR-19a和miR-19b的联合分析对BCR具有预后价值。在PCa中，尿液miRNA检测组合（miR-21、miR-19a和miR-19b）的诊断潜力高于前列腺特异性抗原（PSA）检测（曲线下面积[AUC]=0.738对AUC = 0.514）。
测量尿液中PCa特异性miRNA的水平有助于更特异性地检测PCa并预测BCR。
