Research On Super Enhancer-related Oncogenes Specific To Esophageal Squamous Cell Carcinoma

Background:Esophageal cancer is one of the most common malignant tumor worldwide with morbidity ranking 8th and mortality ranking 6th?About 90%of patients in China are esophageal squamous cell carcinoma(ESCC).Despite significant advances in research of underlying mechanism of esophageal squamous cell carcinoma in recent decades,few significant improvements in overall survival have been achieved.Super enhancers(SEs)are frequently associated with key lineage-specific genes that control cell state and differentiation in normal somatic cells and were found at key oncogenic drivers in many tumor cells.SEs are of enormous potential in identification of driver gene and disease associated variable Site.Objective:To identify SE-associated genes which are differentially expressed and associated with prognosis utilizing the SE landscape established in ESCC cells.Methods:We obtained SE landscape established in ESCC cells lines and ESCC gene expression data published by our laboratory.We distinguished significantly differentially expressed genes and analyzed the biological process and pathway involved.Combined with clinical information of ESCC patients,we conducted multi-factors Cox regression analysis to find independent prognostic factors.Results:162 SE-associated protein coding genes were identified in both ESCC cell lines.The average expression level of SE-associated genes was higher than average expression level of all genes in both tumor tissues and adjacent tissues(p<0.001).Between them,112 genes were differentially expressed.Multi-factors Cox regression analysis indicated TNM staging(p=0.0040,HR=2.77,95%CI[1.38-5.54]),number of metastatic lymph nodes(p=0.0139,HR=1.16,95%CI[1.03-1.30])and expression level of PKP1(p=0.0020,HR=0.715 95%CI[0.57-0.88])were independent prognostic factors.Conclusions:After combining SE landscape in two ESCC cell lines,162 SE-associated protein coding genes were identified and associated with focal adhesion and PI3K/Akt pathway.The average expression level of SE-associated genes was higher than average expression level of all genes in tumor tissues and adjacent tissues.Multi-factors Cox regression analysis indicated TNM staging,number of metastatic lymph nodes and expression level of PKP1 were independent prognostic factors.