Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma

  • Signal Transduct Target Ther. 2022 Feb 25;7(1):53. doi: 10.1038/s41392-022-00873-8.
Yiyi Xi   #  1 ,  Yuan Lin   #  2 ,  Wenjia Guo   #  3 ,  Xinyu Wang  4 ,  Hengqiang Zhao  4 ,  Chuanwang Miao  1 ,  Weiling Liu  1 ,  Yachen Liu  1 ,  Tianyuan Liu  1 ,  Yingying Luo  1 ,  Wenyi Fan  1 ,  Ai Lin  1 ,  Yamei Chen  1 ,  Yanxia Sun  1 ,  Yulin Ma  1 ,  Xiangjie Niu  1 ,  Ce Zhong  1 ,  Wen Tan  1 ,  Meng Zhou  4 ,  Jianzhong Su  5  6 ,  Chen Wu  7  8  9 ,  Dongxin Lin  10  11  12
Affiliations
  • 1. Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 2. Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking University, Beijing, 100871, China.
  • 3. Cancer Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830000, China.
  • 4. School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325011, China.
  • 5. School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325011, China. [email protected].
  • 6. Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, China. [email protected].
  • 7. Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. [email protected].
  • 8. Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China. [email protected].
  • 9. CAMS Key Laboratory of Genetics and Genomic Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. [email protected].
  • 10. Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. [email protected].
  • 11. Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China. [email protected].
  • 12. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, 510060, China. [email protected].
  • # Contributed equally.
PMID: 35210398 DOI: 10.1038/s41392-022-00873-8
Abstract

This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma (ESCC), which if diagnosed at advanced stages has <30% five-year survival rate. Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues, we identified 35,577 differentially methylated CpG sites (DMCs) and characterized their distribution patterns. Integrating whole-genome DNA and RNA-sequencing data of the same samples, we found multiple dysregulated Transcription Factors and ESCC-specific genomic correlates of identified DMCs. Using featured DMCs, we developed a 12-marker diagnostic panel with high accuracy in our dataset and the TCGA ESCC dataset, and a 4-marker prognostic panel distinguishing high-risk patients. In-vitro experiments validated the functions of 4 marker host genes. Together these results provide additional evidence for the important roles of aberrant DNA methylations in ESCC development and progression. Our DMC-based diagnostic and prognostic panels have potential values for clinical care of ESCC, laying foundations for developing targeted methylation assays for future non-invasive Cancer detection methods.

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