Stuopelyte Kristina, Daniunaite Kristina, Bakavicius Arnas, Lazutka Juozas R, Jankevicius Feliksas, Jarmalaite Sonata
Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Sauletekio Avenue 7, Vilnius LT-10222, Lithuania.
Urology Centre, Vilnius University, Santariskiu 2, Vilnius LT-08661, Lithuania.
Br J Cancer. 2016 Sep 6;115(6):707-15. doi: 10.1038/bjc.2016.233. Epub 2016 Aug 4.
In this paper, the utility of urine-circulating microRNAs (miRNAs) as the potential biomarker of prostate cancer (PCa), the second most prevalent male cancer worldwide, was evaluated.
Cancerous (N=56) and non-cancerous (N=16) prostate tissues were analysed on TaqMan Low Density Array, with the initial screening of 754 miRNAs in a subset of the samples. The abundance of selected miRNAs was analysed in urine specimens from two independent cohorts of patients with PCa (N=215 overall), benign prostatic hyperplasia (BPH; N=23), and asymptomatic controls (ASC; N=62) by means of quantitative reverse transcription PCR.
Over 100 miRNAs were found deregulated in PCa as compared with non-cancerous prostate tissue. After thorough validation, four miRNAs were selected for the analysis in urine specimens. The abundance of miR-148a and miR-375 in urine was identified as specific biomarkers of PCa in both cohorts. Combined analysis of urine-circulating miR-148a and miR-375 was highly sensitive and specific for PCa in both cohorts (AUC=0.79 and 0.84) and strongly improved the diagnostic power of the PSA test (AUC=0.85, cohort PCa1), including the grey diagnostic zone (AUC=0.90).
Quantitative measurement of urine-circulating miR-148a and miR-375 can serve as the non-invasive tool for sensitive and specific detection of PCa.
本文评估了尿液循环微RNA（miRNA）作为前列腺癌（PCa）潜在生物标志物的效用，前列腺癌是全球第二常见的男性癌症。
对癌性（N = 56）和非癌性（N = 16）前列腺组织进行TaqMan低密度阵列分析，在一部分样本中初步筛选754种miRNA。通过定量逆转录PCR分析来自两个独立队列的前列腺癌患者（共N = 215）、良性前列腺增生（BPH；N = 23）和无症状对照（ASC；N = 62）尿液样本中选定miRNA的丰度。
与非癌性前列腺组织相比，在前列腺癌中发现超过100种miRNA失调。经过全面验证后，选择了四种miRNA用于尿液样本分析。尿液中miR-148a和miR-375的丰度在两个队列中均被确定为前列腺癌的特异性生物标志物。尿液循环miR-148a和miR-375的联合分析在两个队列中对前列腺癌具有高度敏感性和特异性（AUC = 0.79和0.84），并显著提高了PSA检测的诊断能力（AUC = 0.85，PCa1队列），包括灰色诊断区（AUC = 0.90）。
尿液循环miR-148a和miR-375的定量测量可作为敏感且特异检测前列腺癌的非侵入性工具。
