The Genome-wide DNA methylation changes in gastrointestinal surgery patients with and without postoperative delirium: Evidence of immune process in its pathophysiology

Abstract

AimThe pathophysiological mechanisms of postoperative delirium (POD) are still unclear, and there is no reliable biomarker to distinguish between those with and without POD. Our aim was to discover DNAm markers associated with POD in blood collected from patients before and after gastrointestinal surgery. MethodWe collected blood samples from 16 patients including 7 POD patients at three timepoints; before surgery (pre), the first and third postoperative days (day1 and day3). We measured differences in DNA methylation between POD and control groups between pre and day1 as well as between pre and day3 using the Illumina EPIC array method. Besides, enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also performed after excluding influence of common factors related to surgery and anesthesia. ResultThe results showed that pre and day1 comparisons showed that immune and inflammatory signals such as 'T-cell activation' were significantly different, consistent with our previous studies with non-Hispanic White subjects. In contrast, we found that these signals were not significant any more when pre was compared with day3. ConclusionThese results provide strong evidence for the involvement of inflammatory and immune-related epigenetic signals in the pathogenesis of delirium, including POD, regardless of ethnic background. These findings also suggest that DNAm, which is involved in inflammation and immunity, is dynamically altered in patients with POD. In summary, the present results indicate that these signals may serve as a new diagnostic tool for POD.