The Screening And Preliminary Verification Of Aberrant Methylation Genes In Cutaneous Squamous Cell Carcinoma

Background Cutaneous squamous cell carcinoma(CSCC)is a kind of malignant tumor originated from keratinocytes residing within the epidermis and its appendage.The incidence of CSCC accounts for the second place in skin malignancies,only after skin basal cell carcinoma.The morbidity of the disease is high,and is still rising in the past decades,probably due to its increasing incidence and higher local and distant metastasis rate.Therefore,scientists paid closer attention to its pathogenesis.Epigenetics regulates gene expression mainly by DNA methylation and histone modification without altering the genomic sequence.Changes in DNA methylation status are important carcinogenic factors,including reduction in the overall methylation level of the genome and abnormal increases in local methylation levels in CpG islands,which lead to instability in the genome and negative or decreased expression of tumor suppressor genes.Objective Screen out genes of interestand and validate its epigenetic roles in CSCC.Methods RRBS and RNA-seq techniques were used to sequence DNA methylation and transcriptome of paired CSCC cancerous and adjacent normal tissues,in order to screen out aberrant methylated genes.QPCR was used to verify the mRNA expression levels of genes of interest in a large number of clinical samples.Results A total of 23 genes of interest,e.g.ACACB,were obtained through analyzing the RRBS and RNA-seq data.Preliminary validation results showed that mRNA expression levels of these targeted genes were decreased by use of expanded CSCC clinical samples.Conclusion Aberrant methylation of these genes' promoter regions might be involved in the pathogenesis of CSCC.Further study is needed to investigate the epigenetic function of target genes in CSCC.