Grim Age, Grim Prognosis: Epigenetic Aging Predicts Pancreatic Surgery Risk

Area of Science:

• Oncology
• Epigenetics
• Surgical Outcomes

Background:

• Pancreatic ductal adenocarcinoma (PDAC) resection offers the only cure, but perioperative risks and survival predictions are challenging.
• Existing risk assessments do not adequately predict postoperative complications, adjuvant chemotherapy completion, or overall survival (OS) in PDAC patients.
• Epigenetic age acceleration (EAA) reflects biological aging via DNA methylation and may offer novel predictive insights.

Purpose of the Study:

• To assess the association of EAA, using Horvath, Pheno, and Grim clocks, with OS.
• To evaluate EAA's correlation with postoperative complications.
• To determine EAA's relationship with the failure to complete adjuvant chemotherapy in resectable PDAC.

Main Methods:

• Prospective cohort study of 332 patients undergoing pancreatic surgery for PDAC.
• Exclusion of patients with non-PDAC histology, non-resectable disease, or neoadjuvant chemotherapy.
• DNA methylation analysis of preoperative blood samples using the Infinium MethylationEPIC v2.0 Kit.

Main Results:

• Higher preoperative Grim EAA correlated with reduced overall survival (HR 1.12; P=0.024).
• Increased severe postoperative complications were associated with higher Grim EAA (OR 1.77; P=0.008).
• Failure to complete adjuvant chemotherapy was linked to higher Grim EAA (OR 1.47; P<0.0001).

Conclusions:

• Grim EAA shows potential as a preoperative risk stratification tool for resectable PDAC.
• This epigenetic marker may aid in personalizing treatment strategies for PDAC patients.
• Further validation studies are necessary before clinical implementation of Grim EAA.