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

Jiamin Huang; Yi Chen; Zaiwen Guo; Yanzhen Yu; Yi Zhang; Pingsong Li; Lei Shi; Guozhong Lv; Bingwei Sun

doi:10.1093/burnst/tkac050

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

Burns Trauma. 2023 Jan 15:11:tkac050. doi: 10.1093/burnst/tkac050. eCollection 2023.

Authors

Jiamin Huang¹, Yi Chen², Zaiwen Guo¹, Yanzhen Yu¹, Yi Zhang³, Pingsong Li⁴, Lei Shi⁵, Guozhong Lv⁶, Bingwei Sun¹

Affiliations

¹ Department of Burns and Plastic Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, Jiangsu Province, China.
² Department of Burns and Plastic Surgery, Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China.
³ Department of Burns and Plastic Surgery, Affiliated Hospital of Nantong University, Nantong 226000, Jiangsu, China.
⁴ Department of Burns and Plastic Surgery, Northern Jiangsu People's Hospital, Yangzhou 225001, Jiangsu, China.
⁵ Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China.
⁶ Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214041, Jiangsu, China.

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.

Keywords: Early warning; Integrating multi-omics analysis; Marker; Sepsis; Severe burn.