Ahn Jong-Hyuk, Yi Jin Wook
Department of Surgery, Chung-Ang University Hospital, Seoul, Korea.
Department of Surgery, Inha University College of Medicine, Incheon, Korea.
Updates Surg. 2025 Jun 9. doi: 10.1007/s13304-025-02233-x.
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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染对甲状腺癌在基因组水平上的影响仍知之甚少。我们研究的目的是确定近期感染SARS-CoV-2的患者的甲状腺癌组织中是否发生了显著的DNA甲基化变化。使用DNA甲基化EPIC芯片分析了3例感染新冠病毒的甲状腺乳头状癌（PTC）患者（病例组）和3例疫情前PTC患者（对照组）手术切除的正常甲状腺组织和PTC组织。在正常甲状腺组织和PTC组织中鉴定出差异甲基化探针（DMP）和差异甲基化区域（DMR）。随后进行功能富集分析以探索受影响的途径。感染新冠病毒的PTC组织呈现出独特的DNA甲基化谱，PTC组织中有6848个DMP，而正常甲状腺组织中为140个。SARS-CoV-2感染未通过甲基化显著影响正常甲状腺组织。PTC组织中的SARS-CoV-2感染与肿瘤抑制基因（RUNX3、PAOX）、Wnt信号通路、HOX基因家族、细胞黏附相关基因的高甲基化以及对病毒相关基因反应的低甲基化有关。在PTC中鉴定出的关键DMR包括GPR75、CCDC80和ENTPD3，提示细胞黏附、肿瘤增殖和免疫逃逸发生改变。SARS-CoV-2感染与PTC组织中显著的DNA甲基化改变有关，对肿瘤进展和侵袭性具有潜在影响。这些发现表明新冠病毒可能影响甲状腺癌生物学。需要进一步研究来验证这些表观遗传修饰，建立因果关系并确定其临床相关性。
