Epigenetic analysis reveals aberrant aging in thyroid cancer

Area of Science:

• Endocrinology
• Epigenetics
• Oncology

Background:

• Thyroid cancer (TC) is the most common endocrine malignancy and is associated with aging.
• Epigenetic alterations, including DNA methylation (DNAm) patterns, are implicated in cancer development.
• Understanding the relationship between epigenetic age and TC is crucial for advancing cancer research.

Purpose of the Study:

• To investigate DNA methylation (DNAm) age acceleration in thyroid cancer (TC) tissues compared to adjacent non-cancerous tissues.
• To explore the associations between DNAm age acceleration and genomic, transcriptomic, and immune profiles in TC.
• To determine the relationship between DNAm age and clinicopathological features or survival in TC patients.

Main Methods:

• Utilized TCGA and GSE97466 datasets for DNAm age estimation using Horvath's clock and Bayesian Neural Network (BNN) clock.
• Integrated genomic, transcriptomic, and mutational analyses, including senescence-associated secretory phenotype (SASP), immune cell infiltration, and thyroid differentiation.
• Quantified epigenetic aging in TC and adjacent normal thyroid tissues.

Main Results:

• Demonstrated significant DNAm age acceleration in TC tissues compared to controls.
• Observed a diminished correlation between DNAm age and chronological age in TC tissues (R≈0.62) versus control tissues (R≈0.94).
• Found associations between accelerated DNAm age and higher telomerase gene expression, heightened SASP signaling, elevated M2 macrophages, reduced activated NK cells, BRAF mutations, and lower thyroid differentiation scores (TDS).

Conclusions:

• Thyroid cancer exhibits significant epigenetic age acceleration, suggesting a role for epigenetic dysregulation in its pathogenesis.
• Accelerated DNAm age in TC is linked to distinct molecular and immune profiles, including specific mutations and altered immune cell infiltration.
• These findings highlight the complex interplay of epigenetic regulation, immune dysfunction, and genomic instability in thyroid cancer, paving the way for future research and therapeutic strategies.