Identification of Genes with Altered Methylation and Its Role in Early Diagnosis of Sepsis-Induced Acute Respiratory Distress Syndrome

Abstract

Purpose Early diagnosis of sepsis-induced acute respiratory distress syndrome (ARDS) is critical for effective treatment. We aimed to identify early stage biomarkers. Materials and Methods Differentially expressed genes were identified in whole blood samples from patients with sepsis or ARDS based on the Gene Expression Omnibus (GEO) datasets GSE32707, GSE54514 and GSE10361. Functional enrichment analysis explored the biological characteristics of differentially expressed genes. Genes with high functional connectivity based on a protein-protein interaction network were marked as hub genes, which were validated using the GEO dataset GSE76293, and a gene set variation analysis index (GSVA) was assigned. Diagnostic and predictive ability of the hub genes were assessed by receiver operating characteristic (ROC) curve analysis. DNA methylation levels of hub genes were quantified using the GEO dataset GSE67530. Results Forty-one differentially expressed genes were shared between sepsis-specific and ARDS-specific datasets. MAP2K2 and IRF7 functional activity was highly connected in sepsis-induced ARDS. Hub genes included RETN, MVP, DEFA4, CTSG, AZU1, FMNL1, RBBP7, POLD4, RIN3, IRF7. ROC curve analysis of the hub gene GSVA index showed good diagnostic ability in sepsis or ARDS. Among genes related to sepsis-induced ARDS, 17 were differentially methylated. Principal component analysis and heatmaps indicated that gene methylation patterns differed significantly between ARDS patients and controls. Conclusion We identified a genetic profile specific to early-stage sepsis-induced ARDS. The abnormal expression of these genes may be caused by hypomethylation, which may serve as a biomarker for early diagnosis of ARDS.

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

“…Functional enrichment analysis of 443 DMR-related genes showed that these genes encoded major histocompatibility complex class proteins, methyltransferase, and proteins involved in cell adhesion and connection. However, Feng et al ( 195 ) found a significant difference in methylation patterns in blood DNA samples from patients with acute respiratory distress syndrome (ARDS) caused by sepsis through methylation analysis. These discrepant findings suggested a changed DNA methylome for different statues of sepsis.…”

Screening of Key Genes of Sepsis and Septic Shock Using Bioinformatics Analysis

“…15 Multiple studies have shown that epigenetic alterations in sepsis may affect prognosis and serve as diagnostic biomarkers. 16,17 Improved infection prevention and control strategies are urgently needed to reduce the health care burden associated with the development and progression of sepsis and septic shock, as are approaches to early diagnosis and appropriate treatment. The present study used bioinformatics to explore biomarkers and potential therapeutic targets associated with the development of sepsis.…”

The epigenetic legacy of ICU feeding and its consequences

“…Epigenetic research found its way to the field of critical illness only recently. Whereas initial studies focused on animal models, the last few years epigenetic abnormalities have also been documented in adult and pediatric patients with different types of critical illness, including sepsis [58][59][60][61][62][63][64][65][66] ]. Second, due to the frequent urgency of ICU-admission, it is difficult to establish to what extent epigenetic abnormalities were already preexisting before ICU-admission or occurred de novo.…”

“…Epigenetic research found its way to the field of critical illness only recently. Whereas initial studies focused on animal models, the last few years epigenetic abnormalities have also been documented in adult and pediatric patients with different types of critical illness, including sepsis [58–66], transplant and other major surgery [67,68 ▪ ,69,70 ▪ ], traumatic brain injury (TBI) or other major trauma [71 ▪ ,72,73 ▪ ,74], acute pancreatitis [75], and COVID-19 [76–79,80 ▪ ,81,82,83 ▪ ], as well as in heterogeneous cohorts [84 ▪ ,85–86]. Most studies focused on DNA-methylation [58–60,63–65,67,68 ▪ ,69,70 ▪ ,71 ▪ ,72,73 ▪ ,80 ▪ ,83 ▪ ,84 ▪ ,85–86], but also histone-modification/chromatin-accessibility [58,69,82] and noncoding RNAs [61,62,66,69,74,81] have been investigated.…”