Yiyi Xi,Yuan Lin,Wenjia Guo,Xinyu Wang,Hengqiang Zhao,Chuanwang Miao,Weiling Liu,Yachen Liu,Tianyuan Liu,Yingying Luo,Wenyi Fan ORCID: orcid.org/0000-0002-7875-7404,Ai Lin,Yamei Chen ORCID: orcid.org/0000-0002-9072-5157,Yanxia Sun ORCID: orcid.org/0000-0002-2122-4009,Yulin Ma,Xiangjie Niu,Ce Zhong,Wen Tan,Meng Zhou ORCID: orcid.org/0000-0001-9987-9024,Jianzhong Su,Chen Wu &…Dongxin Lin ORCID: orcid.org/0000-0002-8723-8868

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.

https://doi.org/10.1038/s41392-022-00873-8

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