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.
Highlights
Esophageal squamous-cell carcinoma (ESCC) accounts for 80% of esophageal cancer cases worldwide[1] and has a 5-year survival rate of
Talukdar et al developed a diagnostic 7-CpG panel based on methylation profiling of more than 100 ESCC samples collected from Africa, Asia and South America countries, but they weighted each CpG marker based on gene expression from The Cancer Genome Atlas (TCGA) ESCC patients.[13]
We looked for potential prognosis markers among differentially methylated CpG sites (DMCs) based on how strong they were associated with the overall survival (OS) time of ESCC patients in our sample and the TCGA ESCC sample
Summary
Esophageal squamous-cell carcinoma (ESCC) accounts for 80% of esophageal cancer cases worldwide[1] and has a 5-year survival rate of
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