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狼疮性肾炎患者循环miR-485-5p的诊断意义及其对临床结局的预测价值评估

Diagnostic significance of circulating miR-485-5p in patients with lupus nephritis and its predictive value evaluation for the clinical outcomes.

作者信息

Wu Qinghua, Qin Yanan, Shi Mei, Yan Liping

机构信息

Department of Nephrology, Dongying People's Hospital, Dongying, Shandong, China.

Department of Obstetrics, Dongying People's Hospital, Dongying, Shandong, China.

出版信息

J Chin Med Assoc. 2021 May 1;84(5):491-497. doi: 10.1097/JCMA.0000000000000522.

Abstract

BACKGROUND

Lupus nephritis (LN) is one of the main risk factors contributing to morbidity and mortality of systemic lupus erythematosus (SLE). This study aimed to investigate the potential role of miR-485-5p in human LN.

METHODS

Quantitative real-time polymerase chain reaction was used for the measurement of miR-485-5p levels. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum were determined by enzyme-linked immunosorbent assay. The diagnostic role of miR-485-5p in LN was evaluated by the receiver operating characteristic (ROC) curve. The impact of miR-485-5p on end-stage renal disease (ESRD) was compared by Kaplan-Meier analysis and Cox regression analysis. The target gene was determined by a dual-luciferase reporter assay system.

RESULTS

MiR-485-5p was highly expressed in SLE and LN patients compared with the healthy controls, and LN patients had the highest level of miR-485-5p. The expression level of miR-485-5p in active LN patients was significantly increased compared with that in nonactive cases. MiR-485-5p expression showed a positive correlation with the levels of estimated glomerular filtration rate, serum creatinine, proteinuria, SLE disease activity index score, and inflammatory cytokines. The ROC analysis results indicated that serum miR-485-5p was a promising biomarker for the early diagnosis of LN, and it can distinguish active LN patients from nonactive ones. Phosphatase and tensin homolog was a direct target of miR-485-5p, and negatively associated with serum miR-485-5p levels. More ESRD events were observed in cases with high miR-485-5p expression, miR-485-5p was an independent factor for the risk of ESRD in LN patients.

CONCLUSION

Serum miR-485-5p might be a novel promising diagnostic marker for LN and has potential predictive value for ESRD risk in LN patients.

摘要

背景

狼疮性肾炎(LN)是导致系统性红斑狼疮(SLE)发病和死亡的主要危险因素之一。本研究旨在探讨miR-485-5p在人类LN中的潜在作用。

方法

采用定量实时聚合酶链反应检测miR-485-5p水平。通过酶联免疫吸附测定法测定血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。通过受试者操作特征(ROC)曲线评估miR-485-5p在LN中的诊断作用。通过Kaplan-Meier分析和Cox回归分析比较miR-485-5p对终末期肾病(ESRD)的影响。通过双荧光素酶报告基因检测系统确定靶基因。

结果

与健康对照相比,miR-485-5p在SLE和LN患者中高表达,且LN患者的miR-485-5p水平最高。与非活动期LN患者相比,活动期LN患者中miR-485-5p的表达水平显著升高。miR-485-5p表达与估计肾小球滤过率、血清肌酐、蛋白尿、SLE疾病活动指数评分和炎性细胞因子水平呈正相关。ROC分析结果表明,血清miR-485-5p是LN早期诊断的一个有前景的生物标志物,并且可以区分活动期LN患者和非活动期患者。磷酸酶和张力蛋白同源物是miR-485-5p的直接靶标,且与血清miR-485-5p水平呈负相关。在miR-485-5p高表达的病例中观察到更多的ESRD事件,miR-485-5p是LN患者发生ESRD风险的独立因素。

结论

血清miR-485-5p可能是LN一种新型且有前景的诊断标志物,对LN患者的ESRD风险具有潜在预测价值。

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