Significant difference of differential expression pyroptosis-related genes and their correlations with infiltrated immune cells in sepsis

Wang, Li; Zhang, Jiting; Zhang, Li; Hu, Lingli; Tian, Jianhui

doi:10.3389/fcimb.2022.1005392

Cited by 5 publications

(6 citation statements)

References 49 publications

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“…As a member of the caspase family, caspase-4 cleaves GSDMD via noncanonical inflammasome signaling (30), leading to pyroptosis. Our findings suggest that CASP4 shares the same expression pattern as GSDMD; that is, patients with poor prognoses had lower caspase-4 expression, which is consistent with previous findings (31). ELANE encodes neutrophil elastase, which is secreted by the neutrophils.…”

Section: Discussionsupporting

confidence: 92%

Construction of Sepsis Diagnostic Models and Identification of Macrophage Subpopulations Based on Pyroptosis-Related Genes

Sun

Tao

Ning

et al. 2023

Shock

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Background: Numerous studies have shown that pyroptosis is associated with sepsis progression, which can lead to dysregulated host immune responses and organ dysfunction. Therefore, investigating the potential prognostic and diagnostic values of pyroptosis in patients with sepsis is essential. Methods: We conducted a study using bulk and single-cell RNA sequencing (scRNA-seq) from the Gene Expression Omnibus database to examine the role of pyroptosis in sepsis. Univariate logistic analysis, least absolute shrinkage, and selection operator regression analysis were used to identify pyroptosis-related genes (PRGs), construct a diagnostic risk score model, and evaluate the selected genes' diagnostic value. Consensus clustering analysis was used to identify the PRG-related sepsis subtypes with varying prognoses. Functional and immune infiltration analyses were used to explain the subtypes' distinct prognoses, and scRNA-seq data were used to differentiate immune-infiltrating cells and macrophage subsets and study cell-cell communication. Results: A risk model was established based on 10 key PRGs (NAIP, ELANE, GSDMB, DHX9, NLRP3, CASP8, GSDMD, CASP4, APIP, and DPP9), of which four (ELANE, DHX9, GSDMD, and CASP4) were associated with prognosis. Two subtypes with different prognoses were identified based on the key PRG expressions. Functional enrichment analysis revealed diminished nucleotide oligomerization domain-like receptor pathway activity and enhanced neutrophil extracellular trap formation in the subtype with a poor prognosis. Immune infiltration analysis suggested a different immune status between the two sepsis subtypes, with the subtype with a poor prognosis exhibiting stronger immunosuppression. The single-cell analysis identified a macrophage subpopulation characterized by gasdermin D (GSDMD) expression that may be involved in pyroptosis regulation, which was associated with the prognosis of sepsis. Conclusion: We developed and validated a risk score for sepsis identification based on 10 PRGs, four of which also have potential value in the prognosis of sepsis. We identified a subset of gasdermin D macrophages associated with poor prognosis, providing new insights into the role of pyroptosis in sepsis.

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Section: Discussionsupporting

confidence: 92%

Construction of Sepsis Diagnostic Models and Identification of Macrophage Subpopulations Based on Pyroptosis-Related Genes

Sun

Tao

Ning

et al. 2023

Shock

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“…The present study has some similarities with Wang's study (49), namely, mining the role of pyroptosis-related genes in sepsis patients and constructing a diagnostic model. In addition, both these studies discussed the immune landscape of hub genes.…”

Section: Discussionmentioning

confidence: 59%

Diagnostic and predictive values of pyroptosis-related genes in sepsis

et al. 2023

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BackgroundSepsis is an organ dysfunction syndrome caused by the body’s dysregulated response to infection. Yet, due to the heterogeneity of this disease process, the diagnosis and definition of sepsis is a critical issue in clinical work. Existing methods for early diagnosis of sepsis have low specificity.AimsThis study evaluated the diagnostic and predictive values of pyroptosis-related genes in normal and sepsis patients and their role in the immune microenvironment using multiple bioinformatics analyses and machine-learning methods.MethodsPediatric sepsis microarray datasets were screened from the GEO database and the differentially expressed genes (DEGs) associated with pyroptosis were analyzed. DEGs were then subjected to multiple bioinformatics analyses. The differential immune landscape between sepsis and healthy controls was explored by screening diagnostic genes using various machine-learning models. Also, the diagnostic value of these diagnosis-related genes in sepsis (miRNAs that have regulatory relationships with genes and related drugs that have regulatory relationships) were analyzed in the internal test set and external test.ResultsEight genes (CLEC5A, MALT1, NAIP, NLRC4, SERPINB1, SIRT1, STAT3, and TLR2) related to sepsis diagnosis were screened by multiple machine learning algorithms. The CIBERSORT algorithm confirmed that these genes were significantly correlated with the infiltration abundance of some immune cells and immune checkpoint sites (all P<0.05). SIRT1, STAT3, and TLR2 were identified by the DGIdb database as potentially regulated by multiple drugs. Finally, 7 genes were verified to have significantly different expressions between the sepsis group and the control group (P<0.05).ConclusionThe pyroptosis-related genes identified and verified in this study may provide a useful reference for the prediction and assessment of sepsis.

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“…The top 14 genes were linked with three primary mechanisms: immune regulation and inflammation, sensory transmission and pain perception, cell cycle regulation and proliferation. Immune regulation and inflammation: CR1, PLCG1 and FAS are implicated in immune regulation and inflammatory responses. These genes could be linked to autoimmune skin diseases and inflammatory skin conditions 73–75 Sensory transmission and pain perception: ANO2 and TRPV1 are involved in sensory signal transmission.…”

Section: Resultsmentioning

confidence: 99%

“…These genes could be linked to autoimmune skin diseases and inflammatory skin conditions. [73][74][75] • Sensory transmission and pain perception: ANO2 and TRPV1 are involved in sensory signal transmission. These genes could potentially contribute to skin sensory abnormalities and disorders associated with pain.…”

Section: Mclustermentioning

confidence: 99%

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Liu,

Lu,

Qiu

et al. 2023

International Wound Journal

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Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co‐expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non‐fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.

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Significant difference of differential expression pyroptosis-related genes and their correlations with infiltrated immune cells in sepsis

Cited by 5 publications

References 49 publications

Construction of Sepsis Diagnostic Models and Identification of Macrophage Subpopulations Based on Pyroptosis-Related Genes

Construction of Sepsis Diagnostic Models and Identification of Macrophage Subpopulations Based on Pyroptosis-Related Genes

Diagnostic and predictive values of pyroptosis-related genes in sepsis

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

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