Alterations in global DNA methylation play a critical role in both aging and
cancer, and DNA methylation (DNAm) age drift has been implicated in
cancer risk and pathogenesis. In the present study, we analyzed the TCGA cohort of papillary and
follicular thyroid carcinoma (PTC and
FTC) for their DNAm age and association with clinic-pathological features. In 54 noncancerous thyroid (NT) samples, DNAm age was highly correlated with patient chronological age (R2 = 0.928, p = 2.6 × 10-31), but drifted to younger than chronological age in most specimens, especially those from patients >50 years old. DNAm age in 502
tumors was also correlated with patient chronological age, but to a much lesser extent (R2 = 0.403). Highly drifted DNAm age (HDDA) was identified in 161
tumors, among which were 101 with DNAm age acceleration while 60 with DNAm age deceleration.
Tumors with HDDA were characterized by the robust aberrations in metabolic activities, extracellular microenvironment components and
inflammation/immunology responses, and dedifferentiation. Importantly, HDDA in
tumors independently predicted shorter disease-free survival of patients. Collectively, NT thyroids from TC patients have younger DNAm age, while HDDA frequently occurs in TCs, and contributes to the TC progression and poor patient outcomes. HDDA may serve as a new prognostic factor for TCs.