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miR-193a/WT1/PODXL 轴在特发性膜性肾病风险和预后评估中的应用。

Application of miR-193a/WT1/PODXL axis to estimate risk and prognosis of idiopathic membranous nephropathy.

机构信息

a Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University , Harbin , China.

出版信息

Ren Fail. 2019 Nov;41(1):704-717. doi: 10.1080/0886022X.2019.1642210.

Abstract

This investigation was managed to explore whether miR-193a in combination with two podocytes, namely, Wilms tumor type 1 (WT1) and podocalyxin (PODXL), were feasible in estimating onset and prognosis of idiopathic membranous nephropathy (IMN). We recruited a total of 189 healthy controls and 364 IMN patients, whose urine samples were prepared to measure the expression of miR-193a and PODXL. Meanwhile, renal tissues collected from above-mentioned IMN patients ( = 364) and renal cell carcinoma patients ( = 189) were arranged to determine the expression of WT1. Ultimately, receiver operating characteristic curves were constructed to appraise the performance of miR-193a, WT1, and PODXL in predicting renal survival of IMN patients. The IMN patients were measured with up-regulated miR-193a expression and down-regulated WT1/PODXL expression, when compared with healthy controls ( < 0.05). Moreover, highly expressed miR-193a, lowly expressed WT1/PODXL, elevated amounts of proteinuria (>3.79 g/24 h)/serum creatinine (>174.63 μmol/L), and declined GFR (≤68.13 mL/min/1.73 m) were implicated as prominent biomarkers for the poor renal survival of IMN patients (all  < 0.05). Notably, miR-193a combined with PODXL and WT1 generated optimal effects in differentiating IMN patients from healthy controls (AUC = 0.994) and also in anticipating the renal survival state of IMN patients (AUC = 0.824), when compared with strategies that merely employed ≤2 of the biomarkers. The combination of miR-193a, WT1, and PODXL might serve as a favorable strategy for expecting IMN prognosis.

摘要

这项研究旨在探讨 miR-193a 与两种足细胞标志物(Wilms 肿瘤 1 型(WT1)和 podocalyxin(PODXL))联合检测是否可用于评估特发性膜性肾病(IMN)的发病和预后。

我们共招募了 189 名健康对照者和 364 名 IMN 患者,采集其尿液样本以检测 miR-193a 和 PODXL 的表达水平。同时,收集上述 IMN 患者(n=364)和肾细胞癌患者(n=189)的肾组织,以检测 WT1 的表达水平。最后,构建受试者工作特征曲线以评估 miR-193a、WT1 和 PODXL 预测 IMN 患者肾存活率的性能。

与健康对照组相比,IMN 患者的 miR-193a 表达上调,WT1/PODXL 表达下调(均<0.05)。此外,高表达 miR-193a、低表达 WT1/PODXL、蛋白尿(>3.79g/24h/血清肌酐(>174.63μmol/L)和下降的肾小球滤过率(≤68.13mL/min/1.73m)是 IMN 患者肾存活率不良的显著生物标志物(均<0.05)。值得注意的是,miR-193a 联合 PODXL 和 WT1 在区分 IMN 患者和健康对照者方面(AUC=0.994)以及预测 IMN 患者的肾脏预后方面(AUC=0.824)的效果优于仅使用≤2 种生物标志物的策略。

miR-193a、WT1 和 PODXL 的联合可能是预测 IMN 预后的一种有利策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd24/6711109/d195064f578f/IRNF_A_1642210_F0001_C.jpg

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