Identification of renal ischemia reperfusion injury subtypes and predictive strategies for delayed graft function and graft survival based on neutrophil extracellular trap-related genes

Wu, Jiyue; Zhang, Feilong; Xiang, Zheng; Zhang, Jiandong; Cao, Peng; Sun, Zejia; Wang, Wei

doi:10.3389/fimmu.2022.1047367

Cited by 38 publications

(21 citation statements)

References 57 publications

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“…The murine renal ischemia–reperfusion injury models have been utilized in many studies to validate the results of bioinformatics analysis from transplant patients datasets [ 24 ]. In the light of the previous literature, we chose the murine IRI induced renal fibrosis model.…”

Section: Methodsmentioning

confidence: 99%

Characterizing hub biomarkers for post-transplant renal fibrosis and unveiling their immunological functions through RNA sequencing and advanced machine learning techniques

Niu,

Xu,

Cheuk

et al. 2024

J Transl Med

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Background Kidney transplantation stands out as the most effective renal replacement therapy for patients grappling with end-stage renal disease. However, post-transplant renal fibrosis is a prevalent and irreversible consequence, imposing a substantial clinical burden. Unfortunately, the clinical landscape remains devoid of reliable biological markers for diagnosing post-transplant renal interstitial fibrosis. Methods We obtained transcriptome and single-cell sequencing datasets of patients with renal fibrosis from NCBI Gene Expression Omnibus (GEO). Subsequently, we employed Weighted Gene Co-Expression Network Analysis (WGCNA) to identify potential genes by integrating core modules and differential genes. Functional enrichment analysis was conducted to unveil the involvement of potential pathways. To identify key biomarkers for renal fibrosis, we utilized logistic analysis, a LASSO-based tenfold cross-validation approach, and gene topological analysis within Cytoscape. Furthermore, histological staining, Western blotting (WB), and quantitative PCR (qPCR) experiments were performed in a murine model of renal fibrosis to verify the identified hub genes. Moreover, molecular docking and molecular dynamics simulations were conducted to explore possible effective drugs. Results Through WGCNA, the intersection of core modules and differential genes yielded a compendium of 92 potential genes. Logistic analysis, LASSO-based tenfold cross-validation, and gene topological analysis within Cytoscape identified four core genes (CD3G, CORO1A, FCGR2A, and GZMH) associated with renal fibrosis. The expression of these core genes was confirmed through single-cell data analysis and validated using various machine learning methods. Wet experiments also verified the upregulation of these core genes in the murine model of renal fibrosis. A positive correlation was observed between the core genes and immune cells, suggesting their potential role in bolstering immune system activity. Moreover, four potentially effective small molecules (ZINC000003830276-Tessalon, ZINC000003944422-Norvir, ZINC000008214629-Nonoxynol-9, and ZINC000085537014-Cobicistat) were identified through molecular docking and molecular dynamics simulations. Conclusion Four potential hub biomarkers most associated with post-transplant renal fibrosis, as well as four potentially effective small molecules, were identified, providing valuable insights for studying the molecular mechanisms underlying post-transplant renal fibrosis and exploring new targets.

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Section: Methodsmentioning

confidence: 99%

Characterizing hub biomarkers for post-transplant renal fibrosis and unveiling their immunological functions through RNA sequencing and advanced machine learning techniques

Niu,

Xu,

Cheuk

et al. 2024

J Transl Med

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“…Six PAAD samples from GSE212966 were downloaded to explore the relationship between hub genes and the TME. In addition, we obtained 1184 EMT‐related genes (EMTRGs) from the EMT Gene Database (https://www.nature.com/subjects/epithelial-mesenchymal-transition), and 136 NET‐related genes (NETRGs) from published reference 18 …”

Section: Methodsmentioning

confidence: 99%

“…In addition, we obtained 1184 EMT-related genes (EMTRGs) from the EMT Gene Database (https://www.nature.com/subjects/epithelial-mesenchymal-transition), and 136 NET-related genes (NETRGs) from published reference. 18…”

Section: Sources Of Datamentioning

confidence: 99%

Comprehensive analyses and experimental verification of NETs and an EMT gene signature for prognostic prediction, immunotherapy, and chemotherapy in pancreatic adenocarcinoma

Zhang,

Wang,

2023

Environmental Toxicology

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Pancreatic adenocarcinoma (PAAD) is an aggressive malignancy with high mortality and poor prognosis. Neutrophil extracellular traps (NETs) and the epithelial‐mesenchymal transition (EMT) significantly influence on the progression of various cancers. However, the underlying relevance of NETs‐ and EMT‐associated genes on the outcomes of patients with PAAD remains to be elucidated. Transcriptome RNA sequencing data, together with clinical information and single‐cell sequencing data of PAAD were collected from public databases. In the TCGA‐PAAD cohort, ssGSEA was used to calculate NET and EMT scores. WGCNA was used to determine the key gene modules. A risk model with eight NET‐ and EMT‐related genes (NERGs) was established using LASSO and multivariate Cox regression analysis. Patients in the reduced risk (RR) group showed better prognostic values compared with those in the elevated risk (ER) group. The prognostic model exhibited reliable and robust prediction when validated using an external database. The distributions of risk genes were explored in a single‐cell sequencing data set. Immune infiltration, immune cycle, and immune checkpoints were compared between the RR and ER groups. Moreover, potential chemotherapeutic drugs were examined. DCBLD2 was identified as a key gene in PAAD cell lines by qRT‐PCR, and was highly expressed in PAAD tissues. GSEA demonstrated that DCBLD2 induced the EMT. Transwell assays and western blotting showed that cell invasion and EMT induction were significantly reduced after DCBLD2 knockdown. Collectively, we constructed a prognosis model based on a NET and EMT gene signature, providing a valuable perspective for the prognostic evaluation and management of PAAD patient.

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“…1 Its etiologies are various, but ischemia reperfusion injury is considered as the most important. 2 Unfortunately, DGF is associated with worse short and long term outcomes. 1 Its early prediction is a daily challenge for physicians to increase graft survival and to improve recipient's outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Delayed graft function (DGF) is an early and frequent complication following kidney transplant 1 . Its etiologies are various, but ischemia reperfusion injury is considered as the most important 2 . Unfortunately, DGF is associated with worse short and long term outcomes 1 .…”

Section: Introductionmentioning

confidence: 99%

Early post‐operative lactate increase following kidney transplant is associated with delayed graft function: A retrospective cohort study

Deniau,

Sen,

Chaussard

et al. 2024

Clinical Transplantation

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IntroductionDelayed graft function (DGF) is a frequent complication following kidney transplant. This study aimed to assess the association between early post‐operative lactate variation and DGF.MethodsThis was a single center, retrospective cohort study between February 2021 and December 2022 in Saint–Louis Hospital (APHP, France). Venous lactate levels were measured immediately (H0) and 4 h (H4) after kidney transplant. The primary outcome was the occurrence of DGF (need for renal replacement therapy between transplantation and day 7). Secondary outcome was the occurrence of complications (i.e., death, vascular thrombosis, hemorrhagic shock, urological complications (hematoma, urinoma), local or systemic infection) between transplant and day 7.ResultsTwo hundred 12 patients were included, and 38 (17.9%) developed DGF. Venous lactate variation between H0 and H4 was higher in patients who developed DGF (−30 (IQR −83, −6)% vs. −15 (IQR −62, −11)%, p = .037), but the variation of level was more often positive (corresponding to an increased lactate production over time between H0 and H4) in patients who developed DGF ((28(85%) vs. 94(62%), p = .011). In multivariate logistic regression, positive venous lactate level variation between H0 and H4 was strongly associated with a reduced risk of developing DGF (OR .30 [.09–.79], p = .024). We did not find any association between post‐operative hyperlactatemia and occurrence of complications between transplant and day 7.DiscussionDGF is a frequent complication following kidney transplantation. Its early prediction could help physicians optimize treatment and protect the kidney. Early venous lactate variation after kidney transplant could help to predict the occurrence of DGF.

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Identification of renal ischemia reperfusion injury subtypes and predictive strategies for delayed graft function and graft survival based on neutrophil extracellular trap-related genes

Cited by 38 publications

References 57 publications

Characterizing hub biomarkers for post-transplant renal fibrosis and unveiling their immunological functions through RNA sequencing and advanced machine learning techniques

Characterizing hub biomarkers for post-transplant renal fibrosis and unveiling their immunological functions through RNA sequencing and advanced machine learning techniques

Comprehensive analyses and experimental verification of NETs and an EMT gene signature for prognostic prediction, immunotherapy, and chemotherapy in pancreatic adenocarcinoma

Early post‐operative lactate increase following kidney transplant is associated with delayed graft function: A retrospective cohort study

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