Proteome alterations in human autopsy tissues in relation to time after death

Protein expression is a primary area of interest for routine histological diagnostics and tissue-based research projects, but the limitations of its post-mortem applicability remain largely unclear. On the other hand, tissue specimens obtained during autopsies can provide unique insight into advanced disease states, especially in cancer research. Therefore, we aimed to identify the maximum post-mortem interval (PMI) which is still suitable for characterizing protein expression patterns, to explore organ-specific differences in protein degradation, and to investigate whether certain proteins follow specific degradation kinetics. Therefore, the proteome of human tissue samples obtained during routine autopsies of deceased patients with accurate PMI (6, 12, 18, 24, 48, 72, 96 h) and without specific diseases that significantly affect tissue preservation, from lungs, kidneys and livers, was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the kidney and liver, significant protein degradation became apparent at 48 h. For the lung, the proteome composition was rather static for up to 48 h and substantial protein degradation was detected only at 72 h suggesting that degradation kinetics appear to be organ specific. More detailed analyses suggested that proteins with similar post-mortem kinetics are not primarily shared in their biological functions. The overrepresentation of protein families with analogous structural motifs in the kidney indicates that structural features may be a common factor in determining similar postmortem stability. Our study demonstrates that a longer post-mortem period may have a significant impact on proteome composition, but sampling within 24 h may be appropriate, as degradation is within acceptable limits even in organs with faster autolysis.

Automated summary

Protein expression is a main focus in histological diagnostics and tissue-based research. The post-mortem applicability of protein expression is still unclear. Autopsy tissue specimens provide unique insight into advanced disease states, especially in cancer research. In this study, the maximum post-mortem interval (PMI) suitable for characterizing protein expression patterns was identified. Significant protein degradation was observed in kidneys and livers at 48 hours, while degradation in lungs was detected at 72 hours, suggesting organ-specific degradation kinetics. Proteins with similar post-mortem kinetics are not primarily shared in their biological functions. Structural features may play a role in determining post-mortem stability.