Association Of Histone - Modified Gene Mutation With Differentially Expressed Genes In Esophageal Squamous Cell Carcinoma And Its Effect On Cell Function

Objective:To discover the differentially expressed genes between subgroups of ESCC patient with or without histone modifier mutations and to analyze the functions of these genes; take EP300 mono-allelic knockout as representative of histone modifier mutation and study its impact on ESCC cell line function. Method:We obtained somatic mutation and gene expression data published by The Cancer Genome Atlas (TCGA) project, categorized ESCC samples into subgroups with or without histone modifier mutation. We synergized 4 bioinformatics software to distinguish significantly differentially expressed genes and analyzed the biological process and pathway involved. We compared the proliferation, migration and invasion capability of an EP300 mono-allelic knockout KYSE-150 cell line constructed by our lab with wild type KYSE-150 cell line. Result:129 genes were identified as differentially expressed across histone modifier mutated and wild-type group. Their products were mainly located on plasma membrane and related to signaling transduction and cellular response to stimuli. Pathways influenced included Wnt and p53 signaling pathway. EP300 mono-allelic knockout significantly hampered the migration and invasion of KYSE-150 cell line. Discussion:This research used bioinformatics approaches to identify differentially expressed genes associated with histone modifier mutation and speculated the potential relation between histone modifier mutation and the downregulation of putative tumor suppressor, the enhanced ability to manage oxidative stress and the reduced inhibition of angiogenesis, through which histone modifier mutation may contribute to ESCC tumorigenesis.