Methylomic and transcriptomic characterization of postoperative systemic inflammatory dysregulation

Chris R. Bain, Paul S. Myles, Rachael Taylor, Hugh Trahair, Yin Peng Lee, Larry Croft, Philip J. Peyton, Thomas Painter, Matthew T.V. Chan, Sophie Wallace, Tomás Corcoran, Andrew D. Shaw, Eldho Paul, Mark Ziemann, Kiymet Bozaoglu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)79-98
Number of pages20
JournalTranslational Research
Volume247
Early online date2022
DOIs
Publication statusE-pub ahead of print - 2022

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