期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 7, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-022-00873-8
关键词
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资金
- National Natural Science Foundation of China [81988101]
- National Science Fund for Distinguished Young Scholars [81725015]
- Chinese Academy Medical Sciences Innovation Fund for Medical Sciences [2021-I2M-1-013, 2019-I2M-2-001]
- Beijing Outstanding Young Scientist Program [BJJWZYJH01201910023027]
- National Key R&D Program of China [2021YFC2502000]
This study examines aberrant DNA methylations as potential markers for diagnosis and prognosis of esophageal squamous-cell carcinoma (ESCC). Various differentially methylated CpG sites were identified, and diagnostic and prognostic panels were developed.
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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