1. Academic Validation
  2. 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.
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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