Methylomic and transcriptomic characterization of postoperative systemic inflammatory dysregulation.

2022-09

Bain, Chris R

Myles, Paul S

Taylor, Rachael

Trahair, Hugh

Lee, Yin Peng

Croft, Larry

Peyton, Philip J

Painter, Thomas

Chan, Matthew T V

Wallace, Sophie

Corcoran, Tomás

Shaw, Andrew D

Paul, Eldho

Ziemann, Mark

Bozaoglu, Kiymet

Journal Article

0000-0003-1185-2869

10.1016/j.trsl.2022.04.004

In this study, we define and validate a state of postoperative systemic inflammatory dysregulation (PSID) based on postoperative phenotypic extremes of plasma C-reactive protein concentration following major abdominal surgery. PSID manifested clinically with significantly higher rates of sepsis, complications, longer hospital stays and poorer short, and long-term outcomes. We hypothesized that PSID will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression suggests that dysregulation is mediated at multiple levels within specific gene sets and hence, nonspecific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.

link

Translational Research : the Journal of Laboratory and Clinical Medicine 2022; 247: 79-98

Translational research : the journal of laboratory and clinical medicine