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胸腔积液外泌体和血浆 circRNAs 作为严重肺炎所致急性呼吸窘迫综合征患者的诊断生物标志物。

CircRNAs in BALF exosomes and plasma as diagnostic biomarkers in patients with acute respiratory distress syndrome caused by severe pneumonia.

机构信息

Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.

出版信息

Front Cell Infect Microbiol. 2023 Aug 22;13:1194495. doi: 10.3389/fcimb.2023.1194495. eCollection 2023.

Abstract

BACKGROUND

The transcriptomic studies targeting circular RNAs (circRNAs) in bronchoalveolar lavage fluid (BALF) exosomes of acute respiratory distress syndrome (ARDS) patients caused by severe pneumonia have rarely been reported. This study aimed to screen and validate abnormally expressed circRNAs in exosomes from BALF of patients with ARDS caused by severe pneumonia and then evaluate the diagnostic values of these circRNAs for ARDS.

METHOD

BALF was collected from four patients with ARDS caused by severe pneumonia and four healthy subjects. CircRNA expression profile was obtained by microarray analysis in BALF exosomes of the discovery cohort. The differentially expressed circRNAs in BALF exosomes were verified by real-time quantitative PCR (RT-qPCR) and underwent competitive endogenous RNA (ceRNA) network construction and functional enrichment analysis.

RESULTS

A total of 629 circRNAs were differentially expressed in BALF exosomes between ARDS patients and healthy subjects. Nine differentially expressed circRNAs were validated by RT-qPCR, and seven were consistent with the results of microarray analysis. CeRNA network analysis was performed for hsa_circRNA_002809, hsa_circRNA_042882, and hsa_circRNA_104034. Functional enrichment analysis showed that the target genes were mainly associated with hypoxia-induced damage, inflammatory response, and the HIF-1 signaling pathway. Hsa_circRNA_042882 and hsa_circRNA_104034 can be regarded as promising diagnostic biomarkers for patients with ARDS caused by severe pneumonia, with remarkable sensitivity and specificity of the area under the curve of 0.8050 and 1 or 0.835 and 0.799, respectively.

CONCLUSION

This study obtained circRNA expression profiles of ARDS patients, and hsa_circRNA_042882 and hsa_circRNA_104034 were regarded as promising diagnostic biomarkers for patients with ARDS caused by severe pneumonia.

摘要

背景

针对严重肺炎导致急性呼吸窘迫综合征(ARDS)患者支气管肺泡灌洗液(BALF)外泌体中的环状 RNA(circRNA)进行的转录组学研究鲜有报道。本研究旨在筛选和验证严重肺炎导致的 ARDS 患者 BALF 外泌体中异常表达的 circRNAs,然后评估这些 circRNAs 对 ARDS 的诊断价值。

方法

收集 4 例严重肺炎导致的 ARDS 患者和 4 例健康对照者的 BALF。通过微阵列分析获取发现队列中 BALF 外泌体的 circRNA 表达谱。通过实时定量 PCR(RT-qPCR)验证 BALF 外泌体中差异表达的 circRNAs,并进行竞争性内源性 RNA(ceRNA)网络构建和功能富集分析。

结果

ARDS 患者与健康对照者 BALF 外泌体中共有 629 个 circRNA 差异表达。通过 RT-qPCR 验证了 9 个差异表达的 circRNAs,其中 7 个与微阵列分析结果一致。对 hsa_circRNA_002809、hsa_circRNA_042882 和 hsa_circRNA_104034 进行了 ceRNA 网络分析。功能富集分析表明,这些靶基因主要与缺氧诱导损伤、炎症反应和 HIF-1 信号通路有关。hsa_circRNA_042882 和 hsa_circRNA_104034 可作为严重肺炎导致 ARDS 患者有前途的诊断生物标志物,曲线下面积的敏感性和特异性分别为 0.8050 和 1 或 0.835 和 0.799。

结论

本研究获得了 ARDS 患者的 circRNA 表达谱,hsa_circRNA_042882 和 hsa_circRNA_104034 可作为严重肺炎导致 ARDS 患者有前途的诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1369/10477665/cb45e8991997/fcimb-13-1194495-g001.jpg

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