Identification of liver proteins as biomarker for postmortem diagnosis of heat stroke through proteomics

Recently, the incidence and mortality of heat stroke (HS) have risen catastrophically. However, postmortem diagnosis of HS is challenging owing to the lack of characteristic morphological markers. Liver damage can often serve as a direct cause of death in HS. Therefore, this study aimed to identify protein biomarkers in the liver and to evaluate their utility as diagnostic biomarkers for HS. The morphological and biochemical tests of HS rats models revealed hydropic degeneration, hepatocyte necrosis, and impaired liver function. 283 differentially expressed proteins between the HS and control groups were screened by proteomic analysis. Subsequently, HSPA4, GGCX, and CYP2B6 were selected as candidate biomarkers based on Proteomic results, Western blotting and immunohistochemistry results in HS rats. These three candidate biomarkers were further validated as diagnostic protein biomarkers for HS death based on the immunohistochemistry results of 29 human cases. Finally, receiver operating characteristic analysis indicated that the combination of HSPA4, GGCX and CYP2B6 provided optimal diagnostic efficacy for HS, with an area under the curve of over 0.999. In conclusion, we propose that the integrating morphological findings, liver function analysis, and protein biomarkers (HSPA4, GGCX, and CYP2B6) in liver could be used for HS diagnosis in forensic practices.