Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis

Abstract

Background Early detection, timely diagnosis and rapid response are essential for case management and precautions of burn-associated sepsis. However, studies on indicators for early warning and intervention have rarely been conducted. This study was performed to better understand the pathophysiological changes and targets for prevention of severe burn injuries. Methods We conducted a multi-center, prospective multi-omics study, including genomics, microRNAomics, proteomics and single-cell transcriptomics, in 60 patients with severe burn injuries. A mouse model of severe burn injuries was also constructed to verify the early warning ability and therapeutic effects of potential markers. Results Through genomic analysis, we identified seven important susceptibility genes (DNAH11, LAMA2, ABCA2, ZFAND4, CEP290, MUC20 and ENTPD1) in patients with severe burn injuries complicated with sepsis. Through plasma miRNAomics studies, we identified four miRNAs (hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-451a and hsa-miR-423-5p) that may serve as early warning markers of burn-associated sepsis. A proteomic study indicated the changes in abundance of major proteins at different time points after severe burn injury and revealed the candidate early warning markers S100A8 and SERPINA10. In addition, the proteomic analysis indicated that neutrophils play an important role in the pathogenesis of severe burn injuries, as also supported by findings from single-cell transcriptome sequencing of neutrophils. Through further studies on severely burned mice, we determined that S100A8 is also a potential early therapeutic target for severe burn injuries, beyond being an early warning indicator. Conclusions Our multi-omics study identified seven susceptibility genes, four miRNAs and two proteins as early warning markers for severe burn-associated sepsis. In severe burn-associated sepsis, the protein S100A8 has both warning and therapeutic effects.

Comparison between XGboost model and logistic regression model for predicting sepsis after extremely severe burns

“…[4][5][6] Therefore, preventing sepsis in patients with extremely severe burns is of great clinical importance. [16][17][18][19] In this present study, the incidence rate of sepsis among 103 severely burned patients, was 19%. Identifying risk factors for sepsis in these patients will undoubtedly lead to significant improvements in their outcome.…”

Advances in nanomaterial-targeted treatment of acute lung injury after burns

“…Burns are tissue damage caused by heat (including hot liquids, steam, hot gases, flames, hot metals, etc. ), which mainly affects the skin or mucous membranes and, in severe cases, subcutaneous or submucosal tissues such as muscles, bones, joints, and even internal organs [1,2]. The lung is the organ with the highest and first highest incidence of insufficiency after severe burns [3].…”