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IFI27 可用于预测和评估早产儿呼吸道合胞病毒感染的严重程度。

IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants.

机构信息

Department of Pediatrics, Affiliated Hospital of Yangzhou University, NO.368 Hanjiang Middle Road, Yangzhou, 225000, Jiangsu, China.

Department of Neonatology, Children's Hospital of Soochow University, NO.92 Zhongnan Street, Industrial Park, Suzhou, 215025, Jiangsu, China.

出版信息

Hereditas. 2021 Jan 2;158(1):3. doi: 10.1186/s41065-020-00167-5.

Abstract

BACKGROUND

Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection.

METHODS

Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out.

RESULTS

Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012).

CONCLUSION

IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.

摘要

背景

早产儿是一个特殊的群体,容易受到呼吸道合胞病毒(RSV)感染,由 RSV 引起的下呼吸道感染(LRTIs)可能很严重,甚至危及生命。本研究的目的是确定易感染 RSV 的早产儿的候选基因,为 RSV 感染的发病机制提供新的见解。

方法

从基因表达综合数据库(GEO)下载了包含 183 例 RSV 感染患者和 33 例健康对照者的 3 个数据集(GSE77087、GSE69606 和 GSE41374),筛选出差异表达基因(DEGs)。通过数据库检索基因相互作用(STRING)构建 DEGs 的蛋白质-蛋白质相互作用(PPI)网络。通过 Cytoscape 软件进行模块分析,确定枢纽基因。对 72 例住院婴儿(50 例 RSV 感染患者和 22 例非 RSV 感染患者)进行临床验证,以验证前 5 个枢纽基因的表达水平。进一步比较 RSV 感染婴儿中高表达 IFI27 和低表达 IFI27 的婴儿(定义为高于或低于中位数 mRNA 水平)。最后,进行了聚焦于 IFI27 的基因集富集分析(GSEA)。

结果

共筛选出 4028 个 DEGs,其中选择了 131 个最显著的 DEGs。随后,确定了 13 个枢纽基因,枢纽基因的功能和途径富集主要包括:对病毒的反应、对病毒的防御反应、病毒基因组复制的调节和病毒生命周期的调节。此外,IFI27 在临床验证中被证实表达最显著。当 IFI27 高表达时,与钙信号通路、花生四烯酸代谢、细胞外基质受体相互作用等基因集显著富集。此外,高表达 IFI27 与更严重的病例相关(p=0.041),更需要机械通气(p=0.034),更频繁的住院(p<0.001)和更长的累积住院时间(p=0.012)。

结论

IFI27 可能有助于预测 RSV 感染,并评估早产儿 RSV 感染的严重程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a18/7778825/6ee53ecb7d3c/41065_2020_167_Fig1_HTML.jpg

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