DNA methylation changes in thyroid cancer patients infected with SARS-CoV-2

The impact of SARS-CoV-2 infection on thyroid cancer at the genomic level remains poorly understood. The purpose of our study was to determine whether significant DNA methylation changes occur in thyroid cancer tissues from patients with recent SARS-CoV-2 infection. Surgically resected normal thyroid and Papillary (PTC) tissues from three COVID-19-infected PTC patients (Cases) and three prepandemic PTC patients (Controls) were analyzed using DNA methylation EPIC arrays. Differentially methylated probes (DMPs) and differentially methylated regions (DMRs) were identified in normal thyroid and PTC tissues. Functional enrichment analysis was subsequently performed to explore the affected pathways. COVID-19-infected PTC tissues presented distinct DNA methylation profiles, with 6,848 DMPs in PTC tissues compared with 140 in normal thyroid tissues. SARS-CoV-2 infection did not significantly affect normal thyroid tissue by methylation. SARS-CoV-2 infection in PTC tissues was associated with hypermethylation of tumor suppressor genes (RUNX3, PAOX), the Wnt signaling pathway, the HOX gene family, cell adhesion-related genes and hypomethylation in response to virus-related genes. The key DMRs identified in PTC included GPR75, CCDC80, and ENTPD3, suggesting altered cell adhesion, tumor proliferation, and immune evasion. SARS-CoV-2 infection is linked to significant DNA methylation alterations in PTC tissues, with potential implications for tumor progression and aggressiveness. These findings suggest that COVID-19 may influence thyroid cancer biology. Further research is needed to validate these epigenetic modifications, establish causal relationships and determine their clinical relevance.