Ruan Xianhui, Yang Feng, Li Mengling, Dong Qiman, Hao Weijing, Zhang Wei, Yun Xinwei, Li Dapeng, Zhao Jingzhu, Qin Xuan, Rong Zihan, Guo Taiyan, Wang Lei, Pan Yi, Gao Ming, Zhang Minjie, Zheng Xiangqian
Department of Thyroid and Neck Tumor, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Shanghai RIGEN Biotechnology Co., Ltd., Shanghai, China.
Thyroid. 2025 May 30. doi: 10.1089/thy.2024.0611.
Thyroid cancer is the most common endocrine malignancy, with papillary thyroid cancer (PTC) accounting for ∼80% of all cases. DNA methylation alterations and gene expression changes in cancer, offer valuable insights into tumor biology and serve as potential clinical biomarkers. However, the functional implications of DNA methylation changes in PTC patients, particularly based on multiomics analysis in the Chinese population, remain insufficiently explored. This study aims to investigate the epigenetic signatures of thyroid cancer and identify the DNA methylation biomarkers for diagnosing PTC in Chinese patients. Thyroid cancer tissues ( = 40) and benign thyroid nodule tissues ( = 31) were collected from Chinese patients for global DNA methylation analysis. Gene expression profiles and H3K27ac modifications were also investigated to understand the impacts of epigenetic changes on gene expression. Genome-wide methylation profiling and machine learning methods were employed to differentiate PTC from control samples. Genome-wide DNA methylation maps revealed significant methylome changes in Chinese PTC tissues. By integrating our data with The Cancer Genome Atlas thyroid cancer methylation profiles, we identified unique hypomethylation patterns associated with thyroid hormone synthesis specifically in Chinese PTC patients. RNA sequencing and H3K27ac modification analysis, along with functional assays, showed that the dysregulated genes in PTC patients are critical for the proliferation, migration, and invasion of thyroid cancer. Our study provides a comprehensive view of the multi-omics-based, function-guided DNA methylation landscape for Chinese PTC patients. We identified seven functional differentially methylated regions with high sensitivity and specificity for diagnosing thyroid cancer in Chinese patients. Additionally, is highlighted as a key player in PTC pathogenesis and shows promise as a valuable biomarker for predicting patient outcomes. This research advances our understanding of DNA methylation in thyroid cancer and underscores the importance of developing population-specific diagnostic tools to improve patient outcomes. However, further validation in larger, independent cohorts is needed to confirm their diagnostic value.
甲状腺癌是最常见的内分泌恶性肿瘤，其中甲状腺乳头状癌（PTC）占所有病例的约80%。癌症中的DNA甲基化改变和基因表达变化为肿瘤生物学提供了有价值的见解，并可作为潜在的临床生物标志物。然而，PTC患者中DNA甲基化变化的功能意义，特别是基于中国人群多组学分析的情况，仍未得到充分探索。本研究旨在调查甲状腺癌的表观遗传特征，并识别用于诊断中国患者PTC的DNA甲基化生物标志物。从中国患者中收集甲状腺癌组织（n = 40）和良性甲状腺结节组织（n = 31）用于全基因组DNA甲基化分析。还研究了基因表达谱和H3K27ac修饰，以了解表观遗传变化对基因表达的影响。采用全基因组甲基化谱分析和机器学习方法区分PTC与对照样本。全基因组DNA甲基化图谱显示中国PTC组织中存在显著的甲基组变化。通过将我们的数据与癌症基因组图谱甲状腺癌甲基化谱相结合，我们确定了在中国PTC患者中与甲状腺激素合成特异性相关的独特低甲基化模式。RNA测序和H3K27ac修饰分析以及功能测定表明，PTC患者中失调的基因对甲状腺癌的增殖、迁移和侵袭至关重要。我们的研究提供了基于多组学、功能导向的中国PTC患者DNA甲基化景观的全面视图。我们确定了七个功能差异甲基化区域，对诊断中国患者的甲状腺癌具有高灵敏度和特异性。此外，[此处原文可能有缺失内容]被强调为PTC发病机制中的关键因素，并有望成为预测患者预后的有价值生物标志物。这项研究推进了我们对甲状腺癌中DNA甲基化的理解，并强调了开发针对特定人群的诊断工具以改善患者预后的重要性。然而，需要在更大的独立队列中进一步验证以确认它们的诊断价值。
