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揭示尿路感染的潜在生物标志物:一种综合生物信息学方法。

Unveiling Potential Biomarkers for Urinary Tract Infection: An Integrated Bioinformatics Approach.

作者信息

Maddah Reza, Ghanbari Fahimeh, Veisi Maziyar, Koosehlar Eman, Shadpirouz Marzieh, Basharat Zarrin, Hejrati Alireza, Amiri Bahareh Shateri, Hejrati Lina

机构信息

Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Applied Physiology Research Center, Isfahan University of Medical, Isfahan, Iran.

出版信息

Adv Biomed Res. 2024 Jul 29;13:44. doi: 10.4103/abr.abr_355_23. eCollection 2024.

DOI:10.4103/abr.abr_355_23
PMID:39224398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11368229/
Abstract

BACKGROUND

Urinary tract infections (UTIs) are a widespread health concern with high recurrence rates and substantial economic impact, and they can increase the prevalence of antibiotic resistance. This study employed an integrated bioinformatics approach to identify key genes associated with UTI development, offering potential targets for interventions.

MATERIALS AND METHODS

For this study, the microarray dataset GSE124917 from the Gene Expression Omnibus (GEO) database was selected and reanalyzed. The differentially expressed genes (DEGs) between UTIs and healthy samples were identified using the LIMMA package in R software. In this section, Enrichr database was utilized to perform functional enrichment analysis of DEGs. Subsequently, the protein-protein interaction (PPI) network of the DEGs was constructed and visualized through Cytoscape, utilizing the STRING online database. The identification of hub genes was performed using Cytoscape's cytoHubba plug-in employing various methods. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic accuracy of hub genes.

RESULTS

Among the outcomes of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the tumor necrosis factor (TNF) signaling pathway was identified as one of the notable pathways. The PPI network of the DEGs was successfully established and visualized in Cytoscape with the aid of the STRING online database. Using cytoHubba with different methods, we identified seven hub genes (STAT1, IL6, IFIT1, IFIT3, IFIH1, MX1, and IRF7). Based on the ROC analysis, all hub genes showed high diagnostic value.

CONCLUSION

These findings provide a valuable baseline for future research aimed at unraveling the intricate molecular mechanisms behind UTI.

摘要

背景

尿路感染(UTIs)是一个广泛存在的健康问题,复发率高且具有重大经济影响,还会增加抗生素耐药性的发生率。本研究采用综合生物信息学方法来识别与尿路感染发展相关的关键基因,为干预措施提供潜在靶点。

材料与方法

在本研究中,从基因表达综合数据库(GEO)中选择并重新分析了微阵列数据集GSE124917。使用R软件中的LIMMA软件包识别尿路感染样本与健康样本之间的差异表达基因(DEGs)。在本节中,利用Enrichr数据库对DEGs进行功能富集分析。随后,利用STRING在线数据库构建DEGs的蛋白质-蛋白质相互作用(PPI)网络,并通过Cytoscape进行可视化。使用Cytoscape的cytoHubba插件采用多种方法进行枢纽基因的识别。进行受试者工作特征(ROC)分析以评估枢纽基因的诊断准确性。

结果

在京都基因与基因组百科全书(KEGG)通路分析的结果中,肿瘤坏死因子(TNF)信号通路被确定为显著通路之一。借助STRING在线数据库,成功在Cytoscape中建立并可视化了DEGs的PPI网络。使用不同方法的cytoHubba,我们识别出七个枢纽基因(STAT1、IL6、IFIT1、IFIT3、IFI1H1、MX1和IRF7)。基于ROC分析,所有枢纽基因均显示出较高的诊断价值。

结论

这些发现为未来旨在揭示尿路感染背后复杂分子机制的研究提供了有价值的基线。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/24fffe4f876c/ABR-13-44-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/01e68a1629e4/ABR-13-44-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/95d6f9a24869/ABR-13-44-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/43be21effea2/ABR-13-44-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/19376baeee60/ABR-13-44-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/24fffe4f876c/ABR-13-44-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/01e68a1629e4/ABR-13-44-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/95d6f9a24869/ABR-13-44-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/43be21effea2/ABR-13-44-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/19376baeee60/ABR-13-44-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf0/11368229/24fffe4f876c/ABR-13-44-g005.jpg

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本文引用的文献

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Urinary Tract Infections: The Current Scenario and Future Prospects.尿路感染:当前现状与未来展望
Pathogens. 2023 Apr 20;12(4):623. doi: 10.3390/pathogens12040623.
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Insulin Downregulated the Infection of Uropathogenic (UPEC) in Bladder Cells in a High-Glucose Environment through JAK/STAT Signaling Pathway.胰岛素通过JAK/STAT信号通路下调高糖环境下膀胱细胞中尿路致病性大肠杆菌(UPEC)的感染。
Microorganisms. 2021 Nov 24;9(12):2421. doi: 10.3390/microorganisms9122421.
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Flagella, Type I Fimbriae and Curli of Uropathogenic Promote the Release of Proinflammatory Cytokines in a Coculture System.
尿路致病性细菌的鞭毛、I型菌毛和卷曲菌毛在共培养系统中促进促炎细胞因子的释放。
Microorganisms. 2021 Oct 27;9(11):2233. doi: 10.3390/microorganisms9112233.
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IFIT3 (interferon induced protein with tetratricopeptide repeats 3) modulates STAT1 expression in small extracellular vesicles.IFIT3(干扰素诱导的具有四肽重复的蛋白 3)调节小细胞外囊泡中的 STAT1 表达。
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Phage Therapy as a Novel Strategy in the Treatment of Urinary Tract Infections Caused by .噬菌体疗法作为治疗由……引起的尿路感染的一种新策略。
Antibiotics (Basel). 2020 Jun 5;9(6):304. doi: 10.3390/antibiotics9060304.
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Enhanced uropathogenic Escherichia coli-induced infection in uroepithelial cells by sugar through TLR-4 and JAK/STAT1 signaling pathways.糖通过 TLR-4 和 JAK/STAT1 信号通路增强尿路致病性大肠杆菌引起的尿路上皮细胞感染。
J Microbiol Immunol Infect. 2021 Apr;54(2):193-205. doi: 10.1016/j.jmii.2019.05.008. Epub 2019 Jun 19.
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Alternative treatment approaches of urinary tract infections caused by uropathogenic Escherichia coli strains.由尿路致病性大肠杆菌菌株引起的尿路感染的替代治疗方法。
Acta Biochim Pol. 2019 May 28;66(2):129-138. doi: 10.18388/abp.2018_2787.
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An introduction to the epidemiology and burden of urinary tract infections.尿路感染的流行病学及负担介绍。
Ther Adv Urol. 2019 May 2;11:1756287219832172. doi: 10.1177/1756287219832172. eCollection 2019 Jan-Dec.
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Urinary Tract Infection Antibiotic Resistance in the United States.美国的尿路感染抗生素耐药性
Prim Care. 2018 Sep;45(3):455-466. doi: 10.1016/j.pop.2018.05.005. Epub 2018 Jul 9.
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Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection.白细胞介素-6/Stat3 信号在宿主对抗尿路感染的抗菌反应中起着至关重要的作用。
Kidney Int. 2018 Jun;93(6):1320-1329. doi: 10.1016/j.kint.2017.12.006. Epub 2018 Feb 21.