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长链非编码 RNA、Cox2 和 HOTAIR 血清表达谱在系统性红斑狼疮中作为新型诊断生物标志物的潜在作用。

The potential role of serum expression profile of long non coding RNAs, Cox2 and HOTAIR as novel diagnostic biomarkers in systemic lupus erythematosus.

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt.

Department of Rheumatology and Rehabilitation, Faculty of Medicine, Fayoum University, Fayoum, Egypt.

出版信息

PLoS One. 2022 Aug 16;17(8):e0268176. doi: 10.1371/journal.pone.0268176. eCollection 2022.

Abstract

BACKGROUND

The role of the long non-coding RNAs (lncRNAs) in the pathogenesis of systemic lupus erythematosus (SLE) is mostly unknown, despite increasing evidence that lncRNAs extensively participate in physiological and pathological conditions.

AIM

To detect the level of lncRNA-Cox2, HOTAIR, IL-6, and MMP-9 in the serum of SLE patients and to correlate these levels with disease activity and patients' clinical and laboratory data to evaluate the value of these biomarkers for SLE diagnosis and assessment of disease activity.

METHODS

Blood samples from 58 SLE patients, and 60 healthy controls (HCs) were used for detection of lncRNAs-Cox2 and HOTAIR expression levels by real-time polymerase chain reaction. Both IL-6 and MMP-9 serum levels were assayed by enzyme-linked immunosorbent assay. Lupus activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

RESULTS

The serum expression levels of lncRNA-Cox2 and HOTAIR were significantly up-regulated in SLE patients vs HCs (fold change [median (IQR) was 1.29(0.81-1.71, P<0.0001) and 2.68(0.95-3.67), P = 0.038) for lncRNA-Cox2 and HOTAIR, respectively. Serum levels of both IL-6 and MMP-9 were significantly high in SLE patients compared with HCs (P≤0.001 for each). The up-regulated lncRNA-Cox2 was positively associated with the presence of neurological manifestations in SLE patients (P = 0.007). Furthermore, HOTAIR expression level had significantly positive correlation with IL-6 (r = 0.578, P<0.0001), MMP-9 level (r = 0.762, P<0.0001), nephritis grades (r = 0.296, P = 0.024) and proteinuria (r = 0.287, P = 0.035). LncRNA-Cox2 showed sensitivity and specificity 72.4%, and 100.0% respectively. HOTAIR sensitivity was 60.3%, and specificity was 100.0%. By multiple logistic regression analysis, lncRNA-Cox2 and HOTAIR were found as SLE independent predictors.

CONCLUSION

LncRNA-COX2 and HOTAIR can be used as new non-invasive biomarkers for the diagnosis of SLE.

摘要

背景

长链非编码 RNA(lncRNA)在系统性红斑狼疮(SLE)发病机制中的作用尚不清楚,尽管越来越多的证据表明 lncRNA 广泛参与生理和病理状态。

目的

检测 SLE 患者血清中 lncRNA-Cox2、HOTAIR、IL-6 和 MMP-9 的水平,并将这些水平与疾病活动以及患者的临床和实验室数据相关联,以评估这些生物标志物在 SLE 诊断和疾病活动评估中的价值。

方法

采用实时聚合酶链反应检测 58 例 SLE 患者和 60 例健康对照者(HCs)血清中 lncRNA-Cox2 和 HOTAIR 的表达水平。采用酶联免疫吸附试验检测 IL-6 和 MMP-9 血清水平。采用系统性红斑狼疮疾病活动指数(SLEDAI)评估狼疮活动度。

结果

SLE 患者血清 lncRNA-Cox2 和 HOTAIR 的表达水平明显高于 HCs(倍数变化[中位数(IQR)分别为 1.29(0.81-1.71,P<0.0001)和 2.68(0.95-3.67),P=0.038)。SLE 患者血清中 IL-6 和 MMP-9 水平均显著高于 HCs(P≤0.001)。上调的 lncRNA-Cox2 与 SLE 患者神经系统表现的存在呈正相关(P=0.007)。此外,HOTAIR 表达水平与 IL-6(r=0.578,P<0.0001)、MMP-9 水平(r=0.762,P<0.0001)、肾炎分级(r=0.296,P=0.024)和蛋白尿(r=0.287,P=0.035)呈显著正相关。lncRNA-Cox2 的灵敏度和特异性分别为 72.4%和 100.0%。HOTAIR 的灵敏度为 60.3%,特异性为 100.0%。通过多元逻辑回归分析,lncRNA-Cox2 和 HOTAIR 被发现为 SLE 的独立预测因子。

结论

lncRNA-COX2 和 HOTAIR 可作为 SLE 诊断的新型非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f4/9380942/9cdb55b58107/pone.0268176.g001.jpg

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