Dynamics of Postmortem Gene Expression in Normal and Neoplastic Murine Liver

Area of Science:

• Biomedical Research
• Molecular Biology
• Oncology

Background:

• Postmortem (autopsy) tissues are valuable for research, enabling large sample cohorts.
• Early postmortem cellular stress activates survival genes, many crucial for tumor cell survival.
• Understanding postmortem interval (PMI) effects on gene expression is vital for reliable transcriptomic studies.

Purpose of the Study:

• To investigate the influence of postmortem interval (PMI) duration on gene expression in normal and tumor tissues.
• To analyze gene expression dynamics in hepatocellular carcinoma models over a 24-hour PMI.
• To assess the impact of PMI on specific genes involved in DNA repair and cell cycle regulation.

Main Methods:

• Utilized a chemically induced hepatocellular carcinoma mouse liver model.
• Compared gene expression dynamics of BRCA1, BRCA2, CHEK1, CHEK2, ATM, and CDK12 in paired normal and tumor tissues.
• Employed RT-qPCR analysis over a 24-hour postmortem interval (PMI).

Main Results:

• Normal liver tissue showed significant increases in gene expression over the 24-hour PMI.
• Tumor tissue exhibited relative transcriptional stability with no substantial changes in studied gene levels.
• Expression profiles converged by 24 hours PMI, eliminating initial differences between normal and tumor tissues, despite adequate RNA quality.

Conclusions:

• Standard RNA quality and histology criteria are insufficient to detect critical postmortem molecular changes.
• Minimizing and controlling PMI is crucial for reliable transcriptomic analysis of biobanked oncological samples.
• Postmortem interval duration significantly impacts gene expression, necessitating careful consideration in research design and sample handling.