Epigenetic age and age acceleration analysis demonstrate distinct patterns in sporadic and hereditary NEN, suggesting lower impact of epigenetic alteration or DNA aging in the pathogenesis of hereditary NEN.
Key Findings
Results
DNA methylation age positively correlated with chronological age across all three clock algorithms, with stronger correlations observed in hereditary NEN subgroups.
Correlations were assessed using Horvath multi-tissue, Levine, and Hannum clock algorithms.
For MEN1-related NEN, Horvath clock correlation was r = 0.65, p < 0.001.
For VHL-related NEN, Horvath clock correlation was r = 0.86, p = 0.002.
93 of 96 samples passed quality assessment and were analyzed; 41 sporadic, 42 MEN1-related, and 10 VHL-related NEN.
Results
Epigenetic age acceleration was significantly higher in sporadic NEN compared to hereditary NEN based on chronological age-adjusted epigenetic age.
Comparisons were based on the Hannum clock.
Sporadic vs. MEN1: p = 0.03.
Sporadic vs. VHL: p = 0.0002.
This pattern held across both age-adjusted epigenetic age and raw difference between epigenetic age and chronological age.
Results
Epigenetic age acceleration was significantly higher in sporadic NEN compared to hereditary NEN based on the difference between epigenetic age and chronological age.
Comparisons were based on the Hannum clock.
Sporadic vs. MEN1: p = 0.009.
Sporadic vs. VHL: p = 0.0005.
This metric represents a complementary approach to age-adjusted epigenetic acceleration.
Results
Higher tumor grade (G2/G3 vs. G1) was associated with higher epigenetic age and age acceleration in adult patients with NEN.
Grading was defined according to WHO classification into G1, G2, and G3.
Epigenetic age was higher in G2/G3 vs. G1: p = 0.04.
Epigenetic age acceleration was higher in G2/G3 vs. G1: p = 0.03.
Analysis was conducted in adult patients with NEN.
Methods
The study cohort consisted of 93 analyzable NEN samples with representation across sporadic, MEN1-related, and VHL-related subgroups, with pancreatic NEN comprising the largest anatomical subgroup.
93 of 96 samples passed quality assessment and filtering.
41/93 were sporadic NEN, 42/93 were MEN1-related, and 10/93 were VHL-related.
48/93 (approximately 52%) were pancreatic NEN (PanNEN).
Epigenetic clocks used included Horvath multi-tissue, Levine, and Hannum algorithms.