Identification of TRAF2, CAMK2G, and TIMM17A as biomarkers distinguishing mechanical asphyxia from sudden cardiac death base on 4D-DIA Proteomics: A pilot study

Abstract

In the context of forensic medicine, the differential diagnosis between mechanical asphyxia and sudden cardiac death is very important regarding the establishment of the cause of death. Traditional autopsy findings have generally been very nonspecific; accordingly, highlighting the need for more specific molecular biomarkers. This study employed four-dimensional data-independent acquisition (4D-DIA) proteomics technology, in combination with both animal models and human samples, to conduct a comprehensive protein expression analysis of cardiac tissues, identifying 7557 proteins, among which 142 shared differentially expressed proteins (DEPS) were screened out. Based on the protein interaction network and through rigorous screening, this study identified three proteins, namely TNF receptor-associated factor 2 (TRAF2), Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G), and translocase of inner mitochondrial membrane 17 homolog A (TIMM17A), as biomarkers for differentiating mechanical asphyxia from sudden cardiac death. Further verification using Western Blot (WB) and immunohistochemistry (IHC) proved the differential expression of these biomarkers in both animal and human samples. These findings, besides deepening the molecular understanding of the pathophysiological differences between sudden cardiac death and mechanical asphyxia, also provided new biomarkers for forensic applications that could enable the improvement of accuracy and reliability in the determination of the cause of death.