Non‑invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles.
Non‑invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles.
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DOI：
10.18632/oncotarget.8124
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Bijnsdorp I
中科院分区：
文献类型：
--
作者：
Koppers-Lalic D;Hackenberg M;de Menezes R;Misovic B;Wachalska M;Geldof A;Zini N;de Reijke T;Wurdinger T;Vis A;van Moorselaar J;Pegtel M;Bijnsdorp I
在许多癌症类型中，~ 22个核苷酸长的microrna （miRNA）的表达和功能被解除调控。成熟的mirna可以在生物体液的细胞外囊泡（EVs）中稳定地检测到，因此它们被认为具有巨大的生物标志物潜力。在本研究中，我们研究了mirna在前列腺癌（PCa）患者的尿- ev中与对照男性相比是否具有不同的表达模式。通过下一代测序，我们确定了4名对照男性和9名PCa患者的miRNA表达。在74名患者（26名对照组和48名pca患者）的独立队列中，使用stemloop RT-PCR验证了mirna。在rt - pcr检测成熟miRNA序列的验证研究中，标准作图方案在尿ev中鉴定出bbbb10 PCa相关的miRNA，但miR-21、miR-375和miR-204未能强有力地区分疾病。相反，我们观察到具有3 '端修饰的miRNA亚型（isomir）在对照男性和PCa患者样本之间具有高度歧视性。随后在74名患者的独立组中验证了miR-21、miR-204和miR-375的高差异表达异构体。对3种异构体进行受体工作特征分析，诊断灵敏度为72.9%，特异度为88%，曲线下面积（AUC）为0.866。相比之下，前列腺特异性抗原的AUC为0.707，测量这些mirna的成熟形式的灵敏度为70.8%，特异性为72% （AUC 0.766）。我们认为异构体可能携带歧视性信息，这有助于产生更强的生物标志物。
In many cancer types, the expression and function of ∼22 nucleotide-long microRNAs (miRNA) is deregulated. Mature miRNAs can be stably detected in extracellular vesicles (EVs) in biofluids, therefore they are considered to have great potential as biomarkers. In the present study, we investigated whether miRNAs have a distinct expression pattern in urine-EVs of prostate cancer (PCa) patients compared to control males. By next generation sequencing, we determined the miRNA expression in a discovery cohort of 4 control men and 9 PCa patients. miRNAs were validated by using a stemloop RT-PCR in an independent cohort of 74 patients (26 control and 48 PCa-patients). Whereas standard mapping protocols identified > 10 PCa associated miRNAs in urinary EVs, miR-21, miR-375 and miR-204 failed to robustly discriminate for disease in a validation study with RT-PCR-detection of mature miRNA sequences. In contrast, we observed that miRNA isoforms (isomiRs) with 3′ end modifications were highly discriminatory between samples from control men and PCa patients. Highly differentially expressed isomiRs of miR-21, miR-204 and miR-375 were subsequently validated in an independent group of 74 patients. Receiver-operating characteristic analysis was performed to evaluate the diagnostic performance of three isomiRs, resulting in a 72.9% sensitivity with a high (88%) specificity and an area under the curve (AUC) of 0.866. In comparison, prostate specific antigen had an AUC of 0.707 and measuring the mature form of these miRNAs yielded a lower 70.8% sensitivity and 72% specificity (AUC 0.766). We propose that isomiRs may carry discriminatory information which is useful to generate stronger biomarkers.
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影响因子：
16
作者：
Bijnsdorp IV;Geldof AA;Lavaei M;Piersma SR;van Moorselaar RJ;Jimenez CR
通讯作者：
Jimenez CR
影响因子：
4.8
作者：
Donovan, M. J.;Noerholm, M.;Brown, G. A.
通讯作者：
Brown, G. A.
DOI：
10.1016/s0360-3016(96)00633-5
发表时间：
1997-03-15
影响因子：
7
作者：
DAmico, AV;Whittington, R;Coleman, CN
通讯作者：
Coleman, CN
影响因子：
6.4
作者：
Larne, Olivia;Martens-Uzunova, Elena;Ceder, Yvonne
通讯作者：
Ceder, Yvonne
影响因子：
8.8
作者：
Bryant, R. J.;Pawlowski, T.;Catto, J. W. F.;Marsden, G.;Vessella, R. L.;Rhees, B.;Kuslich, C.;Visakorpi, T.;Hamdy, F. C.
通讯作者：
Hamdy, F. C.