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唾液和唾液腺组织中独特的 microRNA 表达谱可区分原发性干燥综合征患者与非干燥综合征干燥患者。

Distinct microRNA expression profiles in saliva and salivary gland tissue differentiate patients with primary Sjögren's syndrome from non-Sjögren's sicca patients.

机构信息

Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Section for Clinical Oral Microbiology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

J Oral Pathol Med. 2020 Nov;49(10):1044-1052. doi: 10.1111/jop.13099. Epub 2020 Sep 16.

DOI:10.1111/jop.13099
PMID:32799333
Abstract

OBJECTIVES

Increasing evidence suggests that aberrant expression of microRNAs (miRNAs) is involved in the pathogenesis of primary Sjögren's syndrome (pSS). The aim was thus to characterize the miRNA profile in saliva, salivary gland tissue, and plasma from patients with pSS and compare findings with those of patients having Sjögren-like disease (non-pSS). In addition, to correlate miRNA levels and clinicopathological features of pSS.

METHODS

miRNA real-time quantitative polymerase chain reaction was performed on saliva, plasma, and salivary gland tissue samples from 24 patients with pSS and 16 non-pSS in 384-well plates. T test was used for comparison of miRNA profiles, followed by Benjamini-Hochberg correction. The discriminatory power of miRNAs was evaluated by receiver-operating characteristic curves, and Pearson/Spearman correlation was used for correlation analyses.

RESULTS

In saliva, 14 miRNAs were significantly differentially expressed between pSS and non-pSS, including downregulation of the miR-17 family in pSS. In salivary gland tissue of patients with pSS, miR-29a-3p was significantly upregulated. Plasma miRNAs did not differ between the two groups, although the miR-17 family tended to be downregulated. The combination of miR-17-5p and let-7i-5p in saliva yielded an area under curve of 97% (CI 92%-100%). Several miRNAs correlated significantly with one another and with salivary flow rates and histopathology.

CONCLUSION

Our findings indicate that the miRNA expression profile in saliva may enable to discriminate between pSS and non-pSS patients. However, further validation in larger cohorts is needed as well as functional analyses of the miRNAs of interest.

摘要

目的

越来越多的证据表明,微小 RNA(miRNA)的异常表达与原发性干燥综合征(pSS)的发病机制有关。因此,本研究旨在描述 pSS 患者唾液、唾液腺组织和血浆中的 miRNA 谱,并与具有干燥样疾病(非 pSS)的患者进行比较。此外,还分析了 miRNA 水平与 pSS 的临床病理特征的相关性。

方法

采用实时定量聚合酶链反应(PCR)对 24 例 pSS 患者和 16 例非 pSS 患者的唾液、血浆和唾液腺组织样本进行 miRNA 检测。采用 t 检验比较 miRNA 图谱,然后进行 Benjamini-Hochberg 校正。采用受试者工作特征曲线(ROC)评估 miRNA 的鉴别能力,采用 Pearson/Spearman 相关分析进行相关性分析。

结果

在唾液中,pSS 与非 pSS 患者之间有 14 个 miRNA 存在显著差异表达,包括 miR-17 家族在 pSS 中的下调。pSS 患者的唾液腺组织中,miR-29a-3p 显著上调。两组患者的血浆 miRNA 无差异,但 miR-17 家族有下调趋势。唾液中 miR-17-5p 和 let-7i-5p 的组合曲线下面积为 97%(92%-100%)。一些 miRNA 彼此之间以及与唾液流量和组织病理学之间存在显著相关性。

结论

我们的研究结果表明,唾液中的 miRNA 表达谱可能有助于区分 pSS 和非 pSS 患者。然而,还需要在更大的队列中进行进一步验证,以及对有意义的 miRNA 进行功能分析。

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