Human miRNome profiling identifies microRNAs differentially present in the urine after kidney injury.

Human miRNome profiling identifies microRNAs differentially present in the urine after kidney injury.
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DOI:
10.1373/clinchem.2013.210245
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发表时间:
2013-12
期刊:
影响因子:
9.3
通讯作者:
Vaidya VS
Vaidya VS
中科院分区:
医学1区
文献类型:
--
作者:
Ramachandran K;Saikumar J;Bijol V;Koyner JL;Qian J;Betensky RA;Waikar SS;Vaidya VS

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细胞外microRNA(miRNAs)已被提出作为各种疾病状况的潜在稳健和稳定的生物标志物。本研究的主要目的是鉴定尿液中差异发生的miRNA,这些miRNA可作为急性肾损伤(阿基)的潜在生物标志物,因为传统的阿基标志物在诊断的灵敏度、特异性和及时性方面存在局限性。我们分析了来自6名阿基患者和6名健康对照的合并尿液样本中的1809种miRNA。我们分别测量了12个样本中的378种稳定可检测的miRNA,并选择了阿基患者尿液中与非AKI对照个体相比差异最大的前7种miRNA。在更大的阿基患者队列(n = 98:71例重症监护室(ICU)中的阿基患者和27例经活检证实为肾小管损伤的肾移植患者)和无阿基患者(n = 97:74例健康志愿者和23例无阿基的ICU患者)中评估这些miRNA。我们鉴定了4种能够显著区分阿基患者和非阿基个体的miRNA:miR-21(P = 0.0005)、miR-200 c(P < 0.0001)、miR-423(P = 0.001)和miR-4640(P = 0.0355)。这4种miRNA的组合交叉验证ROC曲线下面积为0.91。在224个样品中,关于miRNA分离和逆转录效率的不精确度<9%。在这项研究中,我们确定了人类尿液的整个miRNome,并确定了一组miRNAs,它们是肾损伤的非侵入性检测和诊断敏感指标。
Extracellular microRNAs (miRNAs) have been proposed as potentially robust and stable biomarkers of various disease conditions. The primary objective of this study was to identify miRNAs differentially occurring in the urine that could serve as potential biomarkers of acute kidney injury (AKI), because traditional AKI markers have limitations with respect to sensitivity, specificity, and timeliness of diagnosis. We profiled 1809 miRNAs in pooled urine samples from 6 patients with AKI and from 6 healthy controls. We measured the 378 stably detectable miRNAs in the 12 samples individually and selected the top 7 miRNAs that were most different in the urine of patients with AKI compared with the non-AKI control individuals. These miRNAs were assessed in a larger cohort of patients with AKI (n = 98:71 AKI patients in the intensive care unit (ICU) and 27 kidney transplantation patients with biopsy-proven tubular injury) and patients without AKI (n = 97: 74 healthy volunteers and 23 ICU patients without AKI). We identified 4 miRNAs capable of significantly differentiating patients with AKI from individuals without AKI: miR-21 (P = 0.0005), miR-200c (P < 0.0001), miR-423 (P = 0.001), and miR-4640 (P = 0.0355). The combined cross-validated area under the ROC curve for these 4 miRNAs was 0.91. The imprecision with respect to miRNA isolation and reverse transcription efficiency was <9% across 224 samples. In this study we determined the entire miRNome of human urine and identified a panel of miRNAs that are both detectable noninvasively and diagnostically sensitive indicators of kidney damage.
在快速发展的特发性肺纤维化中的微RNA处理缺陷。
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