Methylomic and transcriptomic characterization of postoperative systemic inflammatory dysregulation

Area of Science:

• Surgical Inflammation
• Genomics
• Systems Biology

Background:

• Postoperative systemic inflammatory dysregulation (PSID) is a critical condition following major abdominal surgery.
• PSID is characterized by extreme C-reactive protein levels and is associated with increased sepsis, complications, and poorer patient outcomes.

Purpose of the Study:

• To define and validate PSID based on C-reactive protein levels.
• To investigate the association between PSID and genome-wide DNA methylation and gene expression patterns.
• To identify potential molecular targets for early detection and treatment of PSID.

Main Methods:

• Defining PSID using extreme postoperative plasma C-reactive protein concentrations.
• Analyzing genome-wide peripheral blood mononuclear cell differential DNA methylation.
• Assessing differential gene expression in immune and metabolic pathways.

Main Results:

• PSID is clinically manifested by higher rates of sepsis, complications, and prolonged hospital stays.
• Altered DNA methylation and differential gene expression were identified in specific immune and metabolic pathways during PSID.
• Findings suggest PSID involves dramatic changes in DNA methylation and gene expression.

Conclusions:

• PSID is a significant clinical state with severe patient outcomes.
• Altered DNA methylation and gene expression are key features of PSID, indicating dysregulation at multiple molecular levels.
• Nonspecific anti-inflammatory treatments may be ineffective; targeted therapies based on molecular changes are warranted.