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

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

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. sujz@wmu.edu.cn.
  • 6 Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, China. sujz@wmu.edu.cn.
  • 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. chenwu@cicams.ac.cn.
  • 8 Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China. chenwu@cicams.ac.cn.
  • 9 CAMS Key Laboratory of Genetics and Genomic Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. chenwu@cicams.ac.cn.
  • 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. lindx@cicams.ac.cn.
  • 11 Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China. lindx@cicams.ac.cn.
  • 12 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, 510060, China. lindx@cicams.ac.cn.
  • # 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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