循环 miR-150、miR-192、miR-200b 和 miR-423-3p 作为慢性移植物功能障碍的非侵入性生物标志物。

Circulating miR-150, miR-192, miR-200b, and miR-423-3p as Non-invasive Biomarkers of Chronic Allograft Dysfunction.

机构信息

Chronic Kidney Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Arch Med Res. 2017 Jan;48(1):96-104. doi: 10.1016/j.arcmed.2017.03.004.

DOI:10.1016/j.arcmed.2017.03.004

PMID:28577875

Abstract

BACKGROUND AND AIMS

Chronic allograft dysfunction (CAD) is the major cause of renal allograft loss and can only be diagnosed by invasive histological examinations. The current study aimed to determine whether or not the circulating miR-125a, miR-150, miR-192, miR-200b, miR-423-3p and miR-433 could serve as predictors of graft outcome in the renal transplant recipients with CAD.

METHODS

To evaluate the expression levels of miRNAs, we used quantitative real-time PCR (qPCR) and analyzed the plasma samples of 53 renal transplant recipients, including: 27 recipients with stable graft function (SGF), 26 recipients with biopsy-proven interstitial fibrosis and tubular atrophy (IFTA) and 15 healthy controls. Possible correlation between the clinicopathological parameters and the studied circulating miRNAs was also evaluated.

RESULTS

miR-150 (p <0.001), miR-192 (p = 0.003), miR-200b (p = 0.048) and miR-423-3p (p <0.001) were differentially expressed between IFTA and SGF plasma samples. Creatinine correlated with miR-192 (r = 0.414, p = 0.036) and miR-423-3p (r = -0.431, p = 0.028). Moreover, the estimated glomerular filtration rate (eGFR) significantly correlated with the circulating miR-192 (r = -0.390, p = 0.049) and miR-423 (r = 0.432, p = 0.028). Receiver operating characteristic (ROC) analysis indicated that four miRNAs possessed the best diagnostic value for discriminating IFTA from SGF recipients with the areas under the curve (AUC) of 0.87 and high sensitivity and specificity values of 78% and 91%, respectively.

CONCLUSIONS

The results suggest that aberrant plasma levels of these miRNAs are associated with the renal allograft dysfunction. Therefore, they are proposed to be considered as potential diagnostic biomarkers for monitoring of renal graft function.

摘要

背景与目的

慢性移植肾失功（CAD）是导致肾移植失败的主要原因，只能通过有创的组织学检查进行诊断。本研究旨在确定循环 miR-125a、miR-150、miR-192、miR-200b、miR-423-3p 和 miR-433 是否可作为 CAD 肾移植受者移植物结局的预测因子。

方法

为了评估 miRNA 的表达水平，我们使用了定量实时 PCR（qPCR），并分析了 53 名肾移植受者的血浆样本，包括 27 名移植肾功能稳定（SGF）受者、26 名经活检证实为间质纤维化和肾小管萎缩（IFTA）的受者和 15 名健康对照者。还评估了临床病理参数与所研究的循环 miRNA 之间的可能相关性。

结果

miR-150（p＜0.001）、miR-192（p=0.003）、miR-200b（p=0.048）和 miR-423-3p（p＜0.001）在 IFTA 和 SGF 血浆样本之间表达差异有统计学意义。肌酐与 miR-192（r=0.414，p=0.036）和 miR-423-3p（r=-0.431，p=0.028）呈正相关。此外，估算的肾小球滤过率（eGFR）与循环 miR-192（r=-0.390，p=0.049）和 miR-423（r=0.432，p=0.028）呈显著负相关。受试者工作特征（ROC）分析表明，4 种 miRNA 对区分 IFTA 与 SGF 受者具有最佳诊断价值，曲线下面积（AUC）为 0.87，灵敏度和特异性值分别为 78%和 91%。