Cell-Free DNA Hypermethylation in Patients with Acute Pancreatitis

Area of Science:

• Biochemistry
• Genetics
• Clinical Diagnostics

Background:

• Cell-free DNA (cfDNA) promoter hypermethylation is a potential biomarker for pancreatic cancer.
• Similar epigenetic alterations may occur in acute pancreatitis (AP).

Purpose of the Study:

• To investigate the longitudinal cfDNA hypermethylation profile in AP patients.
• To compare cfDNA hypermethylation in AP patients versus healthy controls.
• To assess the association between cfDNA hypermethylation and AP severity markers.

Main Methods:

• Prospective longitudinal study design.
• Inclusion of hospitalized AP patients and healthy controls.
• Methylation-specific PCR analysis of a 23-gene panel in plasma at multiple time points (T0, T6W, T6M, T8Y).
• Evaluation of associations with clinical markers: CRP, leukocyte count, creatinine, hospital stay, and complications.

Main Results:

• AP patients exhibited significantly higher mean hypermethylated genes at disease onset (T0) compared to controls (7.4 vs. 3.3; p < 0.01).
• The mean number of hypermethylated genes decreased over time, normalizing by 7-8 years post-onset (T8Y).
• Total hypermethylation positively correlated with CRP (ρ = 0.39), leukocyte count (ρ = 0.35), and hospital stay duration (ρ = 0.27).

Conclusions:

• AP is characterized by significantly elevated cfDNA hypermethylation at disease onset.
• cfDNA hypermethylation levels in AP patients tend to normalize over extended follow-up periods.
• The degree of cfDNA hypermethylation correlates with key indicators of AP severity.