General anesthesia induces acute cell-free DNA methylation changes in peripheral blood

Area of Science:

• Anesthesiology
• Epigenetics
• Genomics

Background:

• General anesthesia (GA) adverse events are common, but underlying mechanisms remain unclear.
• Investigating GA's impact on DNA methylation in cell-free DNA (cfDNA) is crucial for understanding these effects.
• This study focuses on patients undergoing surgery for lung nodules.

Purpose of the Study:

• To evaluate the global effect of GA on cfDNA methylation profiles.
• To identify specific DNA methylation changes induced by GA.
• To explore the association between GA-induced methylation changes and post-operative outcomes.

Main Methods:

• A retrospective cohort study of 1,006 lung nodule patients (pre- and post-anesthesia).
• Targeted bisulfite sequencing of cfDNA to analyze methylation profiles across 12,899 regions and 105,844 CpG sites.
• Development of prediction models using differentially methylated regions (DMRs) with Random Forest.

Main Results:

• Identified 4,562 GA-induced DMRs associated with developmental, cell adhesion, ECM remodeling, and signaling pathways (e.g., PI3K-AKT, RAS/ERK).
• Prediction models using 20 DMRs accurately predicted post-operative coagulation indicators (APTT, INR, D-dimer) and cell counts (neutrophils, monocytes).
• Lower methylation of cg00232606 (DLX-4 gene) correlated with poorer survival in lung cancer patients.

Conclusions:

• GA induces acute DNA methylation changes linked to tissue damage and repair.
• GA-induced methylation changes correlate with post-operative coagulation function.
• These methylation changes represent promising predictive biomarkers for post-surgical coagulation disorders.