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血浆微小RNA谱是一种与慢性血液透析患者尿路上皮癌相关的生物标志物。

Plasma miRNA profile is a biomarker associated with urothelial carcinoma in chronic hemodialysis patients.

作者信息

Chen Chien-Lung, Lin Chen-Huan, Li An-Lun, Huang Chiu-Ching, Shen Biing-Yir, Chiang Yun-Ru, Fang Pei-Luen, Chang Huan-Cheng, Li Kay-Lun, Yang Wu-Chang, Horng Jorng-Tzong, Ma Nianhan

机构信息

Department of Biomedical Sciences and Engineering, Institute of Systems Biology and Bioinformatics, National Central University , Taoyuan , Taiwan.

Division of Nephrology, Department of Medicine, Taiwan Landseed Hospital , Taoyuan , Taiwan.

出版信息

Am J Physiol Renal Physiol. 2019 Jun 1;316(6):F1094-F1102. doi: 10.1152/ajprenal.00014.2019. Epub 2019 Mar 20.

Abstract

The incidence of urothelial carcinoma (UC) is higher in patients undergoing chronic dialysis than in the general population. This study investigated plasma miRNA profiling as the ancillary diagnosis biomarker associated with UC in patients undergoing chronic hemodialysis. We successfully screened out and detected miRNA expression from plasma in eight patients undergoing dialysis through quantitative real-time PCR array analysis and identified eight candidate miRNAs. The candidate miRNAs were then validated using single quantitative RT-PCR assays from 52 plasma samples. The miRNA classifier for ancillary UC detection was developed by multiple logistic regression analyses. Moreover, we validated the classifier by testing another nine samples. Expression levels of miR-150-5p, miR-150-5p/miR-155-5p, miR-378a-3p/miR-150-5p, miR-636/miR-150-5p, miR-150-5p/miR-210-3p, and miR-19b-1-5p/miR-378a-3p were shown to be significantly different between UC and non-UC samples ( = 0.035, 0.0048, 0.016, 0.024, 0.038, and 0.048). Kaplan-Meier curve analysis also showed that low miR-19b-1-5p expression was associated with a worse prognosis ( = 0.0382). We also developed a miRNA classifier based on five miRNA expression levels to predict UC and found that the area under curve was 0.882. The classifier had a sensitivity of 80% (95% confidence interval: 0.5191% to 0.9567%) and a specificity of 83.7% (95% confidence interval: 0.6799% to 0.9381%). This classifier was tested by nine samples with 100% accuracy. The miRNA classifier offers higher sensitivity and specificity than the existing makers. Thus, this approach will improve the prospective diagnosis of UC in patients undergoing chronic hemodialysis.

摘要

慢性透析患者尿路上皮癌(UC)的发病率高于普通人群。本研究调查了血浆miRNA谱作为慢性血液透析患者中与UC相关的辅助诊断生物标志物。我们通过定量实时PCR阵列分析成功筛选并检测了8例透析患者血浆中的miRNA表达,并鉴定出8个候选miRNA。然后使用来自52份血浆样本的单定量RT-PCR测定法对候选miRNA进行验证。通过多元逻辑回归分析开发了用于辅助UC检测的miRNA分类器。此外,我们通过测试另外9个样本对分类器进行了验证。结果显示,UC和非UC样本之间miR-150-5p、miR-150-5p/miR-155-5p、miR-378a-3p/miR-150-5p、miR-636/miR-150-5p、miR-150-5p/miR-210-3p以及miR-19b-1-5p/miR-378a-3p的表达水平存在显著差异(P = 0.035、0.0048、0.016、0.024、0.038和0.048)。Kaplan-Meier曲线分析还表明,miR-19b-1-5p低表达与较差的预后相关(P = 0.0382)。我们还基于5种miRNA表达水平开发了一种miRNA分类器来预测UC,发现曲线下面积为0.882。该分类器的灵敏度为80%(95%置信区间:0.51*91%至0.9567%),特异性为83.7%(95%置信区间:0.6799%至0.9381%)。该分类器经9个样本测试,准确率为100%。该miRNA分类器比现有标志物具有更高的灵敏度和特异性。因此,这种方法将改善慢性血液透析患者UC的前瞻性诊断。

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