Epigenome-wide DNA methylation profiling in septic and non-septic patients with similar infections: Potential use as sepsis biomarkers
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PROVIDER: PRJNA1206135 | ENA |
REPOSITORIES: ENA
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Project description:Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis by assessing a prospective case-control study comparing DNA methylation profiles between patients with community-acquired sepsis and matched controls with similar infections who did not develop sepsis. Blood samples were collected within 24 hours of hospital admission, and DNA methylation was analyzed using Illumina MethylationEPIC 850 v2 arrays and bisulfite pyrosequencing. The discovery cohort (n=32) identified 4,640 differentially methylated positions (DMPs), with notable hypomethylation in immune-related genes. Functional enrichment analysis revealed significant involvement of these genes in immune processes, including neutrophil activation and monocyte differentiation. Key findings highlighted hypomethylation of SERPINA1, AZU1, MPO, and SLX4, which was validated in an independent cohort (n=28). Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and procalcitonin levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858). Our findings suggest that DNA methylation changes, particularly in immune-related genes, could serve as valuable biomarkers for diagnosing sepsis and predicting patient outcomes. Further research is warranted to confirm their clinical utility and explore potential therapeutic targets.
2025-01-24 | GSE285813 | GEO
Project description:IntroductionSepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis.MethodsA prospective case-control study was conducted to compare DNA methylation profiles between patients with community-acquired sepsis and matched controls who had similar infections but did not develop sepsis. Whole blood samples from these patients were analyzed using the Infinium MethylationEPIC v2.0 kit, enabling genome-wide methylation analysis. Selected genes with differential methylation were validated by pyrosequencing.ResultsSignificant differential DNA methylation patterns were identified between septic and non-septic individuals uising. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction. The most prominent findings include the hypomethylation of immune-related genes (SERPINA1, AZU1, MPO, and SLX4), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels. Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858).DiscussionOur results underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.
| S-EPMC11802815 | biostudies-literature
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Experiment Overall Design: Prospective observational study involving microarray-based bioinformatics.
2009-01-05 | E-GEOD-13904 | biostudies-arrayexpress
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Keywords: Normal vs diseased
2008-12-12 | GSE13904 | GEO
Project description:DNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality due to the lack of sensitive diagnostic and prognostic biomarkers. Delay in sepsis diagnosis leads to treatment difficulties and poor outcomes. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. Illumina 450K methylation microarray revealed that the genes involved in transendothelial leukocyte migration were differentially methylated in septic newborns compared to non-septic newborns, especially the Protocadherin Beta group. Genes like ITGB2-AS1, CCS were found to be differentially methylated significantly, which gives the hope of developing novel, potential epigenetic markers for neonatal sepsis. From this study, we conclude that DNA methylation might play crucial functions in the pathophysiology of neonatal sepsis which was obvious from the difference in methylation level among septic and non-septic babies. In future, the potentiality of these epigenetic biomarkers can be studied in large scale with appropriate techniques which will give further in depth knowledge in this context. DNA methylation analysis of three septic newborns and three non-septic newborns were performed with Illumina Infinium HumanMethylation450 BeadChip. Peripheral venous blood sample was collected from the babies during the third day of birth while taking blood for routine investigations. Non-septic babies are babies admitted to NICU and sampled for other minor ailments. Genomic DNA was extracted using QIAmp DNA Blood Mini kit (Qiagen, Hilden, Germany) and bisulfite treated using EZ DNA methylation kit (Zymoresearch, USA).
2014-06-20 | E-GEOD-58651 | biostudies-arrayexpress
Project description:Nowadays, there is no gold standard of sepsis diagnosis, thus there is a challenge to differentiate between shock septic and non-septic shock following a surgery, since patients with both conditions show similar signs and symptoms. In this sense, to get a quick and accurate diagnosis of septic shock is required to allow an immediate and specific treatment for this condition. In this work, we have evaluated the expression profile by microarray analysis from post-surgical septic shock and non-septic shock patients with the aim of proposing a candidate set genes as gold standard to help in distinguishing both conditions.
2020-08-16 | GSE131761 | GEO
Project description:DNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality due to the lack of sensitive diagnostic and prognostic biomarkers. Delay in sepsis diagnosis leads to treatment difficulties and poor outcomes. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. Illumina 450K methylation microarray revealed that the genes involved in transendothelial leukocyte migration were differentially methylated in septic newborns compared to non-septic newborns, especially the Protocadherin Beta group. Genes like ITGB2-AS1, CCS were found to be differentially methylated significantly, which gives the hope of developing novel, potential epigenetic markers for neonatal sepsis. From this study, we conclude that DNA methylation might play crucial functions in the pathophysiology of neonatal sepsis which was obvious from the difference in methylation level among septic and non-septic babies. In future, the potentiality of these epigenetic biomarkers can be studied in large scale with appropriate techniques which will give further in depth knowledge in this context.
2014-06-20 | GSE58651 | GEO
Project description:Septic cardiac dysfunction is a key feature of severe sepsis and septic shock, contributing to multiorgan dysfunction syndrome and death. It has been established that persistent beta adrenergic stimulation is detrimental in sepsis, and that specific beta 1 blockade mitigates excessive systemic inflammation and improves myocardial function. The aim of this study was to investigate the effects of specific beta 1 blocker esmolol on septic mouse myocardium by genomic and proteomic techniques. We also evaluated survival of septic mice and systemic inflammation under esmolol treatment. C57BL/6 mice were rendered septic by 2 models: cecal ligature and perforation (CLP) and intraperitoneal injection of lipopolysaccharides (LPS). Effects of esmolol on myocardium were assessed by microarray technique. Total RNA were isolated and purified from a 30mg sample of the heart of 6 groups of 8 animals, depending on the sepsis model and the treatment. The labeled cDNA from the treated animals were hybridized against the labeled cDNA from the untreated animals with 2 dye-swaps done for each sepsis model.
2015-08-03 | E-GEOD-31175 | biostudies-arrayexpress
Project description:In this project we performed a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via label-free shotgun proteomics. We enrolled adult (≥18 years old) patients with sepsis from community-acquired infections, diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria. Blood samples were obtained within the first 72 hours from the diagnosis of sepsis (sepsis phase) and on de day before ICU discharge (recovery phase). The Control group consisted of age matched healthy volunteers. We excluded subjects with AIDS, advanced cancer, hematological diseases, and pregnancy.
2021-09-07 | PXD023938 | Pride
Project description:Septic cardiac dysfunction is a key feature of severe sepsis and septic shock, contributing to multiorgan dysfunction syndrome and death. It has been established that persistent beta adrenergic stimulation is detrimental in sepsis, and that specific beta 1 blockade mitigates excessive systemic inflammation and improves myocardial function. The aim of this study was to investigate the effects of specific beta 1 blocker esmolol on septic mouse myocardium by genomic and proteomic techniques. We also evaluated survival of septic mice and systemic inflammation under esmolol treatment.
2015-08-03 | GSE31175 | GEO