Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury.
Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury.
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生物信息分析确定败血性休克相关急性肾损伤的潜在生物标志物和治疗靶点
DOI：
10.1186/s41065-021-00176-y
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发表时间：
2021-04-16
期刊：
影响因子：
2.7
通讯作者：
Shang Y
中科院分区：
文献类型：
--
作者：
Tang Y;Yang X;Shu H;Yu Y;Pan S;Xu J;Shang Y
背景脓毒症和脓毒性休克是重症监护病房（ICU）中常见的致死率高、危及生命的疾病。急性肾损伤（acute kidney injury，阿基）是脓毒症常见的并发症，其发生是脓毒症患者预后不良的标志。我们分析了共差异表达基因（co-DEG），以探索脓毒性休克和阿基之间的关系，并揭示潜在的生物标志物和脓毒性休克相关阿基（SSAKI）的治疗靶点。GSE 57065数据集包括28名感染性休克患者和25名健康志愿者，并在休克后0.5、24和48 h内采集血液样本。从26名阿基患者和11名对照患者中收集GSE 30718样本。使用两个数据集识别AKI-DEG和败血性休克-DEG。随后，基因本体论（GO）功能分析，京都基因和基因组百科全书（KEGG）途径富集分析，蛋白质-蛋白质相互作用（PPI）网络分析，以阐明DEG的分子机制。我们还评估了共同DEGs和相应的预测参与脓毒性休克和阿基的miRNA。ResultsWe确定了62 DEGs在阿基标本和888，870，和717 DEGs在脓毒性休克的血液样本在0.5，24和48小时内，分别。EGF和OLFM 4的hub基因可能参与阿基和QPCT的发生，CKAP 4、PRKCQ、PLAC 8、PRC 1、BCL 9 L、ATP 11B、KLHL 2、LDLRAP 1、NDUFAF 1、IFIT 2、CSF 1 R、HGF、NRN 1、GZMB和STAT 4的hub基因可能与脓毒性休克有关。结论感染性休克与急性肾损伤相关，VMP 1、SLPI、PTX 3、TIMP 1、OLFM 4、LCN 2、S100 A9的co-DEG与预测的miRNAs，尤其是miR-29 b-3 p、miR-152- 3 p、miR-223- 3 p的co-DEG偶联，有望成为SSAKI诊断和治疗的新靶点。和S100 A9基因与SSAKI发生发展的新生物标志物显著相关。
BackgroundSepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI).MethodsTwo gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI.ResultsWe identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes ofEGFandOLFM4may be involved in AKI andQPCT,CKAP4,PRKCQ,PLAC8,PRC1,BCL9L,ATP11B,KLHL2,LDLRAP1,NDUFAF1,IFIT2,CSF1R,HGF,NRN1,GZMB, andSTAT4may be associated with septic shock. Besides, co-DEGs ofVMP1,SLPI,PTX3,TIMP1,OLFM4,LCN2, andS100A9coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future.ConclusionsSeptic shock and AKI are related andVMP1,SLPI,PTX3,TIMP1,OLFM4,LCN2, andS100A9genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.
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