Dataset Information

SOX18-associated gene signature predicts sepsis outcome.

ABSTRACT:

Objectives

Sepsis is a critical medical condition associated with an high mortality. Currently, there are no reliable diagnostic or prognostic biomarkers to evaluate sepsis outcomes. SRY (sex-determining region on the Y chromosome)-box transcription factor 18 (SOX18) is an endothelial barrier protective protein, and a decreased level of SOX18 expression is involved in disruption of human endothelial cell barrier integrity. Over-expression of SOX18 attenuates the bacterial lipopolysaccharide (LPS)-mediated disruption of the vascular barrier and is associated with favorable prognosis. The utility of SOX18-related genes as biomarkers in sepsis is uncertain.

Methods

Transcriptomic analysis was used to profile the PBMC samples of patients with sepsis across two Gene Expression Omnibus (GEO) datasets with survival data. An 84-gene signature was derived from discovery datasets that correlated with SOX18 gene expression and sepsis survival.

Results

Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed Th1 and Th2 cell differentiation, Cytokine-cytokine receptor interaction, and T cell receptor signaling pathways as the most significantly enriched KEGG pathways among 84 genes. A severity score based on the gene expression of 84 genes was allocated to each patient. A notable increase was detected in sepsis patients compared to healthy controls in both discovery and validation cohorts. SOX18-associated gene signature discriminated severe cases from mild cases and performed significantly better than both random 84-gene sets from whole genomes or sepsis survival-related genes. Furthermore, we obtained an 18-gene signature from screening these 84 genes in a LASSO model, which performed better in both discovery and validation cohorts.

Conclusions

Data support SOX18-associated gene signatures as a prognostic biomarker for sepsis.

SUBMITTER: Feng A

PROVIDER: S-EPMC8991122 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

SOX18-associated gene signature predicts sepsis outcome.

Feng Anlin A Ma Wenli W Faraj Reem R Black Stephen M SM Wang Ting T

American journal of translational research 20220315 3

<h4>Objectives</h4>Sepsis is a critical medical condition associated with an high mortality. Currently, there are no reliable diagnostic or prognostic biomarkers to evaluate sepsis outcomes. SRY (sex-determining region on the Y chromosome)-box transcription factor 18 (SOX18) is an endothelial barrier protective protein, and a decreased level of SOX18 expression is involved in disruption of human endothelial cell barrier integrity. Over-expression of SOX18 attenuates the bacterial lipopolysacchar ...[more]

PMID: 35422958

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Project description:Sepsis is a major global health problem, causing a significant burden of disease and death worldwide. Risk stratification of sepsis patients, identification of severe patients and timely initiation of treatment can effectively improve the prognosis of sepsis patients. We procured gene expression datasets for sepsis (GSE54514, GSE65682, GSE95233) from the Gene Expression Omnibus and performed normalization to mitigate batch effects. Subsequently, we applied weighted gene co-expression network analysis to categorize genes into modules that exhibit correlation with macrophage activity. To pinpoint macrophage-associated genes (MAAGs), we executed differential expression analysis and single sample gene set enrichment analysis. We then established a prognostic model derived from four MAAGs that were significantly differentially expressed. Functional enrichment analysis and immune infiltration assessments were instrumental in deciphering the biological mechanisms involved. Furthermore, we employed principal component analysis and conducted survival outcome analyses to delineate molecular subgroups within sepsis. Four novel MAAGs-CD160, CX3CR1, DENND2D, and FAM43A-were validated and used to create a prognostic model. Subgroup classification revealed distinct molecular profiles and a correlation with 28-day survival outcomes. The MAAGs risk score was developed through univariate Cox, LASSO, and multivariate Cox analyses to predict patient prognosis. Validation of the risk score upheld its prognostic significance. Functional enrichment implicated ribonucleoprotein complex biogenesis, mitochondrial matrix, and transcription coregulator activity in sepsis, with an immune infiltration analysis indicating an association between MAAGs risk score and immune cell populations. The four MAAGs exhibited strong diagnostic capabilities for sepsis. The research successfully developed a MAAG-based prognostic model for sepsis, demonstrating that such genes can significantly stratify risk and reflect immune status. Although in-depth mechanistic studies are needed, these findings propose novel targets for therapy and provide a foundation for future precise clinical sepsis management.

Dataset Information

SOX18-associated gene signature predicts sepsis outcome.

Objectives

Methods

Results

Conclusions

Publications

SOX18-associated gene signature predicts sepsis outcome.

Similar Datasets

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