Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277, Jiefang Avenue, Wuhan, 430022, China.
Hereditas. 2021 Apr 16;158(1):13. doi: 10.1186/s41065-021-00176-y.
Sepsis 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).
Two 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.
We 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 of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled 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.
Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.
脓毒症和脓毒性休克是具有高死亡率的危及生命的疾病，在重症监护病房（ICU）中。急性肾损伤（AKI）是脓毒症的常见并发症，其发生是脓毒症患者预后不良的标志。我们分析了差异表达基因（co-DEGs），以探讨脓毒性休克与 AKI 之间的关系，并揭示脓毒性休克相关 AKI（SSAKI）的潜在生物标志物和治疗靶点。
从基因表达综合数据库（GEO）中下载了两个基因表达数据集（GSE30718 和 GSE57065）。GSE57065 数据集包括 28 例脓毒性休克患者和 25 例健康志愿者，在休克后 0.5、24 和 48 小时采集血液样本。GSE30718 标本采集自 26 例 AKI 患者和 11 例对照患者。使用两个数据集识别 AKI-DEGs 和脓毒性休克-DEGs。随后，进行基因本体论（GO）功能分析、京都基因与基因组百科全书（KEGG）通路富集分析和蛋白质-蛋白质相互作用（PPI）网络分析，以阐明 DEGs 的分子机制。我们还评估了与脓毒性休克和 AKI 相关的 co-DEGs 和相应预测的 miRNA。
我们在 AKI 标本中鉴定出 62 个 DEGs，在脓毒性休克血液样本中分别在 0.5、24 和 48 小时内鉴定出 888、870 和 717 个 DEGs。EGF 和 OLFM4 的枢纽基因可能与 AKI 有关，而 QPCT、CKAP4、PRKCQ、PLAC8、PRC1、BCL9L、ATP11B、KLHL2、LDLRAP1、NDUFAF1、IFIT2、CSF1R、HGF、NRN1、GZMB 和 STAT4 可能与脓毒性休克有关。此外，VMP1、SLPI、PTX3、TIMP1、OLFM4、LCN2 和 S100A9 的 co-DEGs 与相应的预测 miRNA 相关，特别是 miR-29b-3p、miR-152-3p 和 miR-223-3p，可能是未来 SSAKI 诊断和治疗的有前途的靶点。
脓毒性休克和 AKI 是相关的，VMP1、SLPI、PTX3、TIMP1、OLFM4、LCN2 和 S100A9 基因与参与 SSAKI 发生和发展的新型生物标志物显著相关。
