| Title | Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma |
| Authors | Xi, Yiyi Lin, Yuan Guo, Wenjia Wang, Xinyu Zhao, Hengqiang Miao, Chuanwang Liu, Weiling Liu, Yachen Liu, Tianyuan Luo, Yingying Fan, Wenyi Lin, Ai Chen, Yamei Sun, Yanxia Ma, Yulin Niu, Xiangjie Zhong, Ce Tan, Wen Zhou, Meng Su, Jianzhong Wu, Chen Lin, Dongxin |
| Affiliation | Chinese Acad Med Sci & Peking Union Med Coll, Dept Etiol & Carcinogenesis, Natl Canc Ctr, Natl Clin Res Ctr,Canc Hosp, Beijing 100021, Peoples R China Peking Univ, Beijing Adv Innovat Ctr Genom, Biomed Pioneering Innovat Ctr, Beijing 100871, Peoples R China Xinjiang Med Univ, Affiliated Canc Hosp, Canc Inst, Urumqi 830000, Peoples R China Wenzhou Med Univ, Sch Biomed Engn, Sch Ophthalmol & Optometry, Wenzhou 325011, Peoples R China Wenzhou Med Univ, Eye Hosp, Wenzhou 325011, Peoples R China Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325000, Peoples R China Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Nanjing 211166, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, CAMS Key Lab Genet & Genom Biol, Beijing 100730, Peoples R China Sun Yat Sen Univ, State Key Lab Oncol South China, Canc Ctr, Guangzhou 510060, Peoples R China |
| Keywords | GENE-EXPRESSION TUMOR-SUPPRESSOR UP-REGULATION CANCER AMPHIREGULIN BIOMARKERS HYPERMETHYLATION PATTERNS REGIONS PACKAGE |
| Issue Date | 25-Feb-2022 |
| Publisher | SIGNAL TRANSDUCTION AND TARGETED THERAPY |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/638620 |
| ISSN | 2095-9907 |
| DOI | 10.1038/s41392-022-00873-8 |
| Indexed | SCI(E) |
| Appears in Collections: | 待认领 |
