Multi-Omics-Based Characterization of DNA Methylation Episignatures for Papillary Thyroid Cancer in a Chinese Population.

Journal: Thyroid : official journal of the American Thyroid Association
Published Date: May 30, 2025

Abstract

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.

Authors

  • Xianhui Ruan
    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.
  • Feng Yang
  • Mengling Li
    Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • Qiman Dong
    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.
  • Weijing Hao
    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.
  • Wei Zhang
    The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • Xinwei Yun
    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.
  • Dapeng Li
    Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
  • Jingzhu Zhao
    Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
  • Xuan Qin
    Chinese Evidence-based Medicine Center, Cochrane China Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
  • Zihan Rong
    Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • Taiyan Guo
    Shanghai RIGEN Biotechnology Co., Ltd., Shanghai, China.
  • Lei Wang
    Department of Nursing, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
  • Yi Pan
    Department of Neurosis and Psychosomatic Diseases, Huzhou Third Municipal Hospital, The Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China.
  • Ming Gao
    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • Minjie Zhang
    Department of Radiology, Children's Hospital of Fudan University, No 399, Wan Yuan Road, Minhang District, Shanghai, 201102, China.
  • Xiangqian Zheng
    Department of Ultrasonography, Integrated Traditional Chinese and Western Medicine Hospital, Jilin, China.

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