Screening of Differential DNA Methylation Loci in Colorectal Cancer by Gene Microarray Technique / 胃肠病学

ABSTRACT

Background:DNA methylation is a vital part of epigenetic modification,and is closely related with the development and progress of multiple tumors such as colorectal cancer. However,its mechanism is not fully clarified. Screening specific methylation gene and construct the methylation expression profile of tumor has become the current research hotspot. Aims:To screen the differential methylation loci in colorectal cancer and para-cancerous normal tissue by gene methylation microarray technique,and to construct specific differential methylation gene profile of colorectal cancer. Methods:Methylation 450K bead-chip was applied to detect the methylation status in colorectal cancer and para-cancerous normal tissues of 6 cases. A total of 431 467 loci were analyzed and compared. Aberrant methylation loci were screened according to P value,and the hypermethylation loci and hypomethylation loci were differentiated by delta beta value. Moreover,the function of differential methylation gene was further analyzed by GO analysis and KEGG analysis. Results:A total of 3 649 differential methylation loci were found by comparing colorectal cancer tissue and para-cancerous normal tissue,including 1 259 hypermethylation loci,which mainly located in promoter and genosome,and 2 390 hypomethylation loci,which mainly located in intergenic region and genosome. A panel of aberrant methylation gene loci was screened out,including hypermethylation gene loci such as SLC15A3 and hypomethylation gene loci such as ACOT2,TTLL8 and UHRF1. GO analysis and KEGG analysis showed that the function of these genes might be correlated with DNA binding,transcription factor activity and signal transduction pathway. Conclusions:There are many differential methylation loci in colorectal cancer and para-cancerous normal tissues,suggesting that aberrant DNA methylation is closely related with the development and progress of colorectal cancer. DNA methylation microarray technique could be applied for preliminary screening of differential methylation loci. However,constructing the differential methylation profile in colorectal cancer as a clinical biomarker should be further validated.