Study On Screening Aberrant Methylation Genes In Esophageal Squamous Cell Carcinoma For Kazakh Nationality In Xinjiang

Objective: To screen the aberrant methylation genes in esophageal squamous cellcarcinoma for Kazakh nationality in Xinjiang. The aberrant DNA methylation genesscreened in this study provides a theoretical basis for deeply study on esophagealsquamous cell carcinoma mechanism.Method: Using Illumina Human Methylation450Kchip to carry out the genome-wide methylation screening on6cancer tissues and6adjacent normal tissues of esophageal squamous cell carcinoma in Kazakh people, and toexplore aberrant the methylation genes. Genome-wide sequencing were carried out on2cancer tissues and2adjacent normal tissues of esophageal squamous cell carcinoma inKazakh people by Hiseq2000. Meanwhile, mRNA database was established. Afterassociation study between the methylation profile and expression profile, aberrant DNAmethylation genes were detected and were uploaded to the GoMiner and the KEGGdatabase, completing the bioinformatic analysis.Results:(1) Compared with adjacentnormal tissues, there were227hypermethylation genes in cancer tissue (χ~2=1050,P<2.2e-16), while only6hypomethylated genes in cancer tissue (χ~2=335.9, P<2.2e-16).(2)2369locus were detected having significant differences between cancer tissue andadjacent normal tissue (P<0.05). mRNA expression varied from0.0312to8192in cancertissue and from0.0312to1024in adjacent normal tissue.(3) The results of associationstudy between methylation profile and expression profile indicate that there were80locus,45down-regulation genes in negative group (r=-0.7920, P=2.2e-16) and10locus，10genes hypermetylated in promoter region，including RAPGEFL1，ALDH1L1，KIAA1522，TP53AIP1，TRIM29，LRRFIP1，PAX9，DUOXA2，CAPN1，HSPB. Additionally, therewere11locus,10up-regulated genes in negative group (r=0.3463,P=7.588e-07)including FRMD4A，NID2，COL23A1，BAI1，CECR2，GNA12，RASA3，DCHS1，ATP10A， ADAMTS16.(4) Using GoMiner to do GO analysis on aberrant DNAmethylation genes, it reveals that RAPGEFL1，TP53AIP1，KIAA1522，DUOXA2were not involved in any biological processe. ALDH1L1ralated to Folinic acid catabolism.LRRFIP1involved in negative transcriptional regulation. CAPN1was associated withpositive regulation of cell proliferation. TRIM29related to positive regulation of Wntpathyway. PAX9was associated with tooth abnormalities. HSPB6involved information oflens.Using KEGG database to do pathyway analysis, we obtained that ALDH1L1involvedin one carbon metabolism and CAPN1participate in the apoptosis process. Conclusion:we screened20abrrent methylation genes,and established the abrrent DNA methylationprofiles for ESCC in Kazakh nationality.The occurrence of ESCC is associated with somebiological processes，such as one carbon metabolism,apoptosis.