Identifying changes in immune cells and constructing prognostic models using immune-related genes in post-burn immunosuppression

Abstract

Background Burn patients are prone to infection as well as immunosuppression, which is a significant cause of death. Currently, there is a lack of prognostic biomarkers for immunosuppression in burn patients. This study was conducted to identify immune-related genes that are prognosis biomarkers in post-burn immunosuppression and potential targets for immunotherapy. Methods We downloaded the gene expression profiles and clinical data of 213 burn patients and 79 healthy samples from the Gene Expression Omnibus (GEO) database. Immune infiltration analysis was used to identify the proportion of circulating immune cells. Functional enrichment analyses were carried out to identify immune-related genes that were used to build miRNA-mRNA networks to screen key genes. Next, we carried out correlation analysis between immune cells and key genes that were then used to construct logistic regression models in GSE77791 and were validated in GSE19743. Finally, we determined the expression of key genes in burn patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results A total of 745 differently expressed genes were screened out: 299 were up-regulated and 446 were down-regulated. The number of Th-cells (CD4+) decreased while neutrophils increased in burn patients. The enrichment analysis showed that down-regulated genes were enriched in the T-cell activation pathway, while up-regulated genes were enriched in neutrophil activation response in burn patients. We screened out key genes (NFATC2, RORA, and CAMK4) that could be regulated by miRNA. The expression of key genes was related to the proportion of Th-cells (CD4+) and survival, and was an excellent predictor of prognosis in burns with an area under the curve (AUC) value of 0.945. Finally, we determined that NFATC2, RORA, and CAMK4 were down-regulated in burn patients. Conclusion We found that NFATC2, RORA, and CAMK4 were likely prognostic biomarkers in post-burn immunosuppression and potential immunotherapeutic targets to convert Th-cell dysfunction.

Molecular imbalance mechanism of skin and blood leucocytes in severe burn patients at different burn times

“…In addition, the MAPK signaling pathway also plays an important role in the process of burn injury ( 24 , 25 ). These inflammatory mediators and signaling pathways can also be targets for burn treatment ( 26 ). Burn injury causes changes in the transcriptome of 80% of leukocytes, which stimulates innate genes (pro - and anti-inflammatory cytokines) and inhibits adaptive immune responses ( 27 ).…”

Systemic immune response of burns from the acute to chronic phase

“…Expression of key genes was associated with the percentage of Th cells (CD4+) and survival and was a good predictor of burn prognosis. 56 In addition, proteomic analysis showed that hemoglobin Subunit α 1(HBA1), Transthyretin (TTR), and Serpin Family F Member 2 (SERPINF2) correlated with mortality outcomes, and are promising markers for the future. 57 These genetic and protein expression information are mainly studies that capture changes in the acute phase and support the immune response that has been discussed above.…”

Screening CEACAM8 and LCN2 as immune-related diagnostic biomarkers after burn to prevent serious complications

“…Besides, preceding researches have illustrated that more than 60% of deaths in burn patients are associated with infection-related complications, primarily on account of antibiotic resistance. Immune disorder after burn is an signi cant reason of infection [3]. Therefore, screening diagnostic markers of burn immune dysfunction can be used to prevent serious complications and death.…”