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

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

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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.

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