Dysregulation of Vitamin D and Its Signaling in Hashimoto's Thyroiditis in Korean Population

Hahimoto's thyroiditis (HT) is the most common thyroid disease leads to hypothyroid in developed countries. Recent studies highlighted the Vitamin D as the potential risk factor or the therapeutic agents for the HT due to its role in modulating immune responses, while the concrete evidence has not been presented. Patients eligible for the surgery of papillary thyroid cancer (PTC) with or without HT were recruited for the study. We analyzed serum thyroid biomarkers including serum vitamin D, anti-TG, anti-TPO for HT patients. Using the RNA-seq the gene expression profile of thyroid tissue, potential correlation between HT and vitamin D or its signaling was investigated. HT cohort showed common clinical characteristics known for the HT in serum biomarkers and enrichment analysis of BP terms and KEGG pathways. Serum vitamin D level was significantly lower in HT patients. However, vitamin D receptor (VDR) expression and genes involved in vitamin D-associated BP terms were significantly upregulated in HT. Real-time PCR and Immunofluorescence staining confirmed enhanced VDR expression throughout the thyroid tissue of HT cohort. This study demonstrated dysregulated vitamin D signaling in thyroid tissue of HT cohort. Further study need to be performed to elucidate etiology, susceptibility, and development of HT in relation with vitamin D signaling. Overall design: RNA-seq profiling of isolated thyroid tissue from papillary thyroid cancer (PTC) patients eligible for surgery with or without HT etiology.

桥本甲状腺炎（Hashimoto's Thyroiditis, HT）是发达国家中引发甲状腺功能减退症的最常见甲状腺疾病。近期研究指出，维生素D因其在调节免疫应答中的作用，可能成为HT的潜在风险因子或治疗制剂，但目前尚无确凿证据支持这一观点。
本研究招募了符合甲状腺乳头状癌（Papillary Thyroid Cancer, PTC）手术指征的患者，无论是否合并HT，均纳入研究队列。我们对HT患者的血清甲状腺生物标志物进行了分析，涵盖血清维生素D、抗甲状腺球蛋白抗体（anti-TG）与抗甲状腺过氧化物酶抗体（anti-TPO）。通过RNA测序（RNA-seq）分析甲状腺组织的基因表达谱，探究HT与维生素D或其信号通路间的潜在关联。HT队列的血清生物标志物符合桥本甲状腺炎的典型临床特征，本研究同时对生物学过程（Biological Process, BP）术语及京都基因与基因组百科全书（KEGG）通路开展了富集分析。结果显示，HT患者的血清维生素D水平显著降低。然而，HT患者甲状腺组织中维生素D受体（VDR）的表达，以及参与维生素D相关BP术语的基因均显著上调。实时荧光定量PCR与免疫荧光染色证实了HT队列甲状腺组织中VDR表达的增强。
本研究证实HT队列甲状腺组织中存在维生素D信号通路失调。未来需开展进一步研究，以阐明HT的病因、易感性及疾病进展与维生素D信号通路的关联。
整体实验设计：对符合手术指征的甲状腺乳头状癌（PTC）患者（合并或不合并HT病因）的分离甲状腺组织进行RNA测序分析。