The Role Of Heat Shock Protein 90α As A New Diagnostic And Prognostic Biomarker Of Sepsis

Objective: To explore the clinical utility of serum heat shock protein 90alpha(HSP90α)in the diagnosis and prognosis of sepsis,and to explore the underlying mechanism.Methods:1.The relevent data of 50 healthy controls and 150 patients with sepsis in a tertiary Hospital in Dali from September 2019 to September 2020 were collected.General clinical data of all the study subjects such as name,sex,age,time of admission,basic diseases,sequential organ failure assessment(SOFA)score were recorded and compared statistical analysis.2.Based on the 28‐days follow-up,we divided the sepsis patients into survival group(n=94)and non‐survival group(n=56).A peripheral venous blood sample was collected from each patient within the first 48?hours of admission.Each blood sample underwent routine laboratory tests,date for blood routine,liver and renal function,CRP,PCT and SOFA were recorded,and the differences between the two groups were compared.3.HSP90α levels in the patients serum were assayed by the enzyme linked immunosorbent assay(ELISA)method.Differences of the HSP90α expressing level in survival group and non‐survival group were compared.4.The diagnostic and prognostic values of each laboratory indicator for sepsis were evaluated using the receiver operating characteristic(ROC)curves.5.All sepsis patients were followed up for 28 days,Kaplan‐Meier curves were used to assess differences in survival between different groups.6.The expression of cytokines(IL-1β,IL-18)and chemokines(MIP-3α,ENA-78)were simultaneously examined by using flow cytometry.The differences of expression for each cytokine/chemokine were compared between survival group and non‐survival group.7.The diagnostic and prognostic values of cytokines(IL-1β,IL-18)and chemokines(MIP-3α,ENA-78)for sepsis were evaluated using the receiver operating characteristic(ROC)curves,and compared with HSP90α.8.Logistic regression models were used to assess independent risk factors for sepsis prognosis.9.The correlation between HSP90α and SOFA score,PCT,IL-1β,IL-18,MIP-3αand ENA-78 were analyzed by Pearson correlation test.Results:1.The white blood cell count,neutrophil count,lymphocyte count,monocyte count,hematocrit,platelet count and HSP90α levels of the sepsis group were significantly higher than those in healthy control group(P<0.05).2.The levels of procalcitonin,SOFA score,creatinine,blood urea nitrogen and HSP90α in the non‐survival group were significantly higher than those in the survival group(P<0.05).3.Among all the indexes,HSP90α had the best prognostic value for sepsis.The area under the curve(AUC)was the largest up to 0.84 [95% CI(0.77‐0.90),P<0.001],the diagnostic sensitivity and the specificity were 98.2% and 63.8% respectively.Survival analysis showed that the higher the level of HSP90α,the higher the 28-day mortality of patients with sepsis(P<0.05).4.The levels of cytokines IL‐1β,IL‐18,chemokine MIP‐3α and ENA‐78 in the non‐survival group were significantly higher than those in the survival group(P<0.05).5.Among cytokines and chemokines,IL ‐ 18 has the best prognostic value for sepsis.The area under the curve(AUC)is the largest up to 0.66 [95% CI(0.57‐0.73),P=0.002],the diagnostic sensitivity and the specificity were 50.0% and 83.0%respectively.6.Logistic regression analysis showed that SOFA score,HSP90α and IL‐18 were independent risk factors for sepsis.7.Correlation analysis showed that the level of HSP90α was positively correlated with the levels of SOFA,IL‐1β,IL‐18 and MIP‐3α.Conclusion:1.HSP90α levels is of substantial value for the diagnosis and prognosisof sepsis,and can be used as a new biomarker for the diagnosis and prognosis of sepsis.2.The ROC curve model showed the optimal cut-off value of HSP90α is 120ng/m L,that sepsis patients with higher expression levels of HSP90α often receive a poor prognosis and a high case fatality rate.3.In prognosis of sepsis the cytokine IL-10 showed the best AUC values,IL-1 βhas no obvious good effect as a prognostic factor among sepsis patients.4.SOFA score,HSP90α,IL‐18 have been documented as independent risk factors for prognosis of sepsis.5.Significant positive correlations were found for HSP90α with SOFA score,PCT,IL‐18,IL‐1β,MIP‐3α.6.Furthermore,HSP90α may be related to the cytokine storm syndrome.