Identification Of Six Serum Markers In Patients With TBI And Their Clinical Role In Predicting Prognosis

Background:Traumatic brain injury(TBI)has become an increasing serious public health problem which has not been fully studied,especially the pathophysiological mechanism during TBI and novel biomolecular markers that can be accurately and widely applied in clinical practice.Previous studies on biomarkers of TBI have not been well applied to clinical evaluation and treatment due to limitations in specificity,sensitivity and other related aspects.Objective:based on the detection of blood biomarkers,this study attempts to deeply understand the pathophysiological mechanism of biological TBI,explore new biomarkers and evaluate their clinical value in predicting prognosis in TBI patients.Methods:In this study,we established a mouse model of ischemia/reperfusion(I/R)brain injury using a transient middle cerebral artery occlusion(tMCAO)method.After then,RNA-sequencing of frontal lobes was performed to screen key inducers during TBI.To further validate the selected genes,we collected Peripheral Blood Mononuclear Samples(PBMCs)from patients with TBI who attended to the Intensive Care Unit(ICU)of Affiliated Hospital of ×× University via central venous catheter,then analyzed gene expression using RT-qPCR strategies,and finally applied ROC curves and co-expression analysis to evaluate the predictive value of the selected genes.Results:Based on its novelty in TBI and its influence in neuroinflammation,excitatory neurotoxicity,oxidative stress,destruction of the blood brain barrier,cell necrosis and apoptosis signaling,a total of 8 genes were screened from RNA sequencing:TGM1,TGM2,ATF3,RCN3,ORAI1,ITPR3,NF-κB1,and RELA.RT-qPCR analysis of PBMC showed that this 8 genes were upregulated during TBI compared with healthy volunteers who went to the hospital for physical examination.The p-values were<0.0001,<0.0001,<0.0001,0.0002,0.0106,0.0002,<0.0001,0.0264,respectively.The area under the ROC curve(AUC)was 0.972,0.951,0.986,0.962,0.729,0.896,0.979 and 0.764,respectively.Conclusion:Novel TBI markers of TGM1,TGM2,ATF3,RCN3,ORAI1 and ITPR3 were proposed,and the value of these genes in assessing the progression and prognosis of TBI was confirmed.