Signal Transduction and Targeted Therapy (Feb 2022)

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

  • Yiyi Xi,
  • Yuan Lin,
  • Wenjia Guo,
  • Xinyu Wang,
  • Hengqiang Zhao,
  • Chuanwang Miao,
  • Weiling Liu,
  • Yachen Liu,
  • Tianyuan Liu,
  • Yingying Luo,
  • Wenyi Fan,
  • Ai Lin,
  • Yamei Chen,
  • Yanxia Sun,
  • Yulin Ma,
  • Xiangjie Niu,
  • Ce Zhong,
  • Wen Tan,
  • Meng Zhou,
  • Jianzhong Su,
  • Chen Wu,
  • Dongxin Lin

DOI
https://doi.org/10.1038/s41392-022-00873-8
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 13

Abstract

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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.