Multi-omics data analysis reveals the complex roles of age in differentiated thyroid cancer.

ABSTRACT

Aims: Age is a major risk factor for differentiated thyroid cancer (DTC); however, the mechanisms underlying aging-regulated progression of DTC remains unclear. Methods: Based on multi-omics data (transcriptional files, somatic mutation files, methylation files) derived from the TCGA database, we comprehensively investigated the genomic and biological features associated with aging in patients with DTC. Results: We confirmed that age was an independent risk factor for overall survival and progression-free survival of patients with DTC, and confirmed that 55 years of age (adopted in the 8th AJCC staging system) is an appropriate cutoff for patients with DTC rather than 45 years (adopted in the 7th AJCC staging system). Using 55 years as the cutoff, we demonstrated DNA methylation-driven transcriptional regulation during aging, and identified the landscape of somatic mutations in young and old patients with DTC along with two aging-related mutations TTN and EIF1AX. Subsequently, we investigated the infiltration of immune cells in DTC, and found that old patients exhibited decreased CD8+ T cells infiltration with lower cytotoxicity. Finally, we constructed a prognosis prediction model based on three age-related genes (PTK2B, E2F1, and GHR) that showed satisfactory performance in predicting patients prognosis. Conclusions: We comprehensively investigated the complex interplay between age and biological features of DTC, which may provide new insights into the role of aging in DTC.