Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Tang, Yun; Yang, Xiaobo; Shu, Huaqing; Yuan, Yu; Pan, Shangwen; Xu, Jiqian; Shang, You

doi:10.1186/s41065-021-00176-y

Cited by 35 publications

(26 citation statements)

References 47 publications

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“…Tang et al [ 38 ] explored the relationship between septic shock and AKI by analyzing codifferentially expressed genes (co-DEGs) in the hope of identifying possible genetic markers for septic shock-associated AKI. They downloaded two gene expression datasets (GSE30718 and GSE57065).…”

Section: Discussionmentioning

confidence: 99%

Identification of Nine mRNA Signatures for Sepsis Using Random Forest

Zhou

Dong²,

Wang

et al. 2022

Computational and Mathematical Methods in Medicine

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Sepsis has high fatality rates. Early diagnosis could increase its curating rates. There were no reliable molecular biomarkers to distinguish between infected and uninfected patients currently, which limit the treatment of sepsis. To this end, we analyzed gene expression datasets from the GEO database to identify its mRNA signature. First, two gene expression datasets (GSE154918 and GSE131761) were downloaded to identify the differentially expressed genes (DEGs) using Limma package. Totally 384 common DEGs were found in three contrast groups. We found that as the condition worsens, more genes were under disorder condition. Then, random forest model was performed with expression matrix of all genes as feature and disease state as label. After which 279 genes were left. We further analyzed the functions of 279 important DEGs, and their potential biological roles mainly focused on neutrophil threshing, neutrophil activation involved in immune response, neutrophil-mediated immunity, RAGE receptor binding, long-chain fatty acid binding, specific granule, tertiary granule, and secretory granule lumen. Finally, the top nine mRNAs (MCEMP1, PSTPIP2, CD177, GCA, NDUFAF1, CLIC1, UFD1, SEPT9, and UBE2A) associated with sepsis were considered as signatures for distinguishing between sepsis and healthy controls. Based on 5-fold cross-validation and leave-one-out cross-validation, the nine mRNA signature showed very high AUC.

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Section: Discussionmentioning

confidence: 99%

Identification of Nine mRNA Signatures for Sepsis Using Random Forest

Zhou

Dong²,

Wang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Pietrukaniec et al [11] believe that miR-29a and miR-10a-5p can be adopted to predict the mortality of patients with SI-AKI in 28 days. Tang et al [12] have pointed out that miR-29b-3p, miR-152-3p, and miR-223-3p all are probably crucial therapeutic targets for SI-AKI. Bioinformatics analysis revealed significantly downregulated miR-4299 and miR-16-5p in sepsis cases [13], which suggested the potential of the two as biomarkers for early diagnosis and risk stratification of SI-AKI.…”

Section: Introductionmentioning

confidence: 99%

Evaluation Value of Serum miR-4299 and miR-16-5p in Risk Stratification of Sepsis-Induced Acute Kidney Injury

Pan¹,

Zhang²,

Hu³

et al. 2022

BioMed Research International

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Objective. This study was designed to determine the evaluation value of serum miR-4299 and miR-16-5p in risk stratification of sepsis-induced acute kidney injury (SI-AKI). Methods. A total of 115 sepsis patients were enrolled and assigned to the SI-AKI group ( n = 64 ) or the sepsis-non-AKI group ( n = 51 ) based on the occurrence of AKI, and 72 healthy individuals were enrolled. Fasting venous blood was sampled from every patient before admission, before therapy, and after therapy, followed by quantification of miR-4299 and miR-16-5p by fluorescence quantitative PCR. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of serum miR-16-5p and miR-4299 expression in predicting SI-AKI, and Pearson’s correlation analysis was performed to explore the associations of the two with Scr, Cys-C, and KIM-1. Results. Cases with sepsis, especially SI-AKI, presented significantly downregulated serum miR-4299 and miR-16-5p. After therapy, the expression in them increased. The area under curve (AUC) of serum miR-4299 and miR-16-5p in the prediction value for early diagnosis of SI-AKI was 0.895 (95% CI: 0.839-0.951, cutoff value: 0.780) and 0.838 (95% CI: 0.767-0.909, cutoff value: 0.775), respectively, and the AUC of them in the prediction value for clinical efficacy on the disease were 0.733 (95% CI: 0.645-0.820, cutoff value: 1.115) and 0.776 (95% CI: 0.698-0.855, cutoff value: 1.125), respectively. Serum miR-16-5p and mIR-4299 were negatively correlated with Scr, Cys-C, and KIM-1, separately. Conclusion. Both miR-16-5p and mIR-4299 are promising factors for early diagnosis of SI-AKI and dynamic evaluation of the efficacy on it.

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“…Our results found that circPTK2 was mainly localized in the cytoplasm. Then we were inspired to predict the miRs bound to circPTK2, of which miR-29b-3p is involved in the incidence and progression of acute kidney injury elicited by sepsis [46]. The target relation between circPTK2 and miR-29b-3p was verified by dual-luciferase reporter gene assay and RIP assay.…”

Section: Discussionmentioning

confidence: 99%

CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1

Xi¹,

Fu²,

Li³

2021

Int Arch Allergy Immunol

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Objective: Sepsis is a predominant reason for the growing morbidity and mortality in the world. The role of circular RNAs (CircRNAs) is actively researched in sepsis. In this study, we attempt to find out the effect of CircRNA protein tyrosine kinase 2 (circPTK2) on cardiomyocyte apoptosis in septic mice. Methods: Septic mouse model was established by cecal ligation and puncture. Then circPTK2 expression was detected and the role of circPTK2 in myocardial damage was assessed after circPTK2 expression was silenced using Ad-sh-circHIPK3. The subcellular localization of circPTK2 was analyzed. Besides, the binding relation between circPTK2 and microRNA (miR)-29b-3p and between miR-29b-3p and BCL2 antagonist/killer 1 (BAK1) was verified. The expression of miR-29b-3p and BAK1 in the myocardium was detected. Functional rescue was conducted to evaluate the role of miR-29b-3p and BAK1 in cardiomyocyte apoptosis in septic mice. Results: CircPTK2 was highly expressed in the myocardium of septic mice, while circPTK2 silencing relieved the cardiac function and reduced inflammatory reaction and cardiomyocyte apoptosis of septic mice. Mechanically, circPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level. Inhibition of miR-29b-3p and BAK1 overexpression could counteract the protective role of circPTK2 silencing in the myocardium of septic mice. Conclusion: CircPTK2 is overexpressed in the myocardium of septic mice. CircPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level, to promote cardiomyocyte apoptosis, inflammatory response, and myocardial damage of the myocardium of septic mice.

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Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Cited by 35 publications

References 47 publications

Identification of Nine mRNA Signatures for Sepsis Using Random Forest

Identification of Nine mRNA Signatures for Sepsis Using Random Forest

Evaluation Value of Serum miR-4299 and miR-16-5p in Risk Stratification of Sepsis-Induced Acute Kidney Injury

CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1

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