尿液循环微RNA在前列腺癌检测中的应用
The utility of urine-circulating miRNAs for detection of prostate cancer.
作者信息
Stuopelyte Kristina, Daniunaite Kristina, Bakavicius Arnas, Lazutka Juozas R, Jankevicius Feliksas, Jarmalaite Sonata
机构信息
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.
出版信息
Br J Cancer. 2016 Sep 6;115(6):707-15. doi: 10.1038/bjc.2016.233. Epub 2016 Aug 4.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
Quantitative measurement of urine-circulating miR-148a and miR-375 can serve as the non-invasive tool for sensitive and specific detection of PCa.
背景
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。
方法
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。
结果
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）。
结论
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。
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