Circulating microRNAs in extracellular vesicles as potential biomarkers for psoriatic arthritis in patients with psoriasis

Circulating microRNAs in extracellular vesicles as potential biomarkers for psoriatic arthritis in patients with psoriasis
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DOI:
10.1111/jdv.16203
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发表时间:
2020-02-27
影响因子:
9.2
通讯作者:
Sonkoly, E.
Sonkoly, E.
中科院分区:
医学2区
文献类型:
--
作者:
Pasquali, L.;Svedbom, A.;Sonkoly, E.

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背景银屑病关节炎(PsA)发生在30%的银屑病患者中。PsA的诊断具有挑战性,临床上没有可靠的分子标记物。MicroRNA是一种短的非编码调节RNA,可被包装到细胞外囊泡(EV)中并分泌到循环系统中,目的探讨血浆EV microRNA是否可作为银屑病患者银屑病A的生物标志物。使用miRCURYTM外泌体分离试剂盒分离血浆EV。RNA测序用于鉴定发现阶段中差异表达的EV miRNA(PsC,n = 15; PsA,n = 14)。在验证阶段(PsC,n = 29; PsA,n = 28),通过qPCR分析血浆EV中的41种选择的miRNA。结果在发现队列中,共检测到19个EV miRNA,其水平在PsA和PsC之间存在显著性差异。在验证队列中证实了PsA与PsC相比血浆EV let-7 b-5 p和miR-30 e-5 p水平显著较低,并且发现其水平降低与PsA的存在相关。ROC曲线分析显示let-7 b-5 p和miR-30 e-5 p的AUC分别为0.68(95%CI 0.53-0.83)和0.69(95%CI 0.55-0.84)。这项探索性研究的结果表明,循环EV microRNA可能作为银屑病患者关节炎的生物标志物。
Background Psoriatic arthritis (PsA) develops in 30% of patients with psoriasis. The diagnosis of PsA is challenging, and there are no reliable molecular markers in clinical use. MicroRNAs are short non-coding regulatory RNAs, which can be actively packaged into extracellular vesicles (EVs) and secreted to the circulation.Objectives To explore whether plasma-derived EV microRNAs may serve as biomarkers for PsA in patients with psoriasis.Methods Plasma samples were obtained from patients with cutaneous-only psoriasis (PsC) and patients with psoriasis and PsA. Plasma EVs were isolated using miRCURY (TM) Exosome Isolation Kit. RNA sequencing was used to identify differentially expressed EV miRNAs in the discovery phase (PsC, n = 15; PsA, n = 14). In the validation phase (PsC, n = 29; PsA, n = 28), 41 selected miRNAs were analysed in plasma EVs by qPCR. The association of the identified miRNAs with PsA was assessed by logistic regression analysis.Results RNA sequencing identified 19 plasma EV miRNAs with significantly different levels between PsA and PsC in the discovery cohort. Significantly lower levels of plasma EV let-7b-5p and miR-30e-5p in PsA vs. PsC were confirmed in the validation cohort, and their decreased levels were found to be associated with the presence of PsA. ROC analysis revealed an AUC of 0.68 (95% CI 0.53-0.83) for let-7b-5p and 0.69 (95% CI 0.55-0.84) for miR-30e-5p.Conclusions Circulating EV microRNA levels are altered in patients with PsA as compared with PsC. Findings of this exploratory study suggest that circulating EV microRNAs may serve as biomarkers for arthritis in psoriasis patients.