| Objective: In this study,through whole-gene methylation,transcriptome detection and targeted validation of cancer and adjacent tissues of gastric cancer in plateau area,the general situation of DNA methylation of gastric cancer in plateau area and its role in gastric cancer were discussed,and potential diagnostic and therapeutic markers of methylated gastric cancer were screened.Methods: 1.Genome-wide methylation sequencing was performed on 5 pairs of gastric cancer tissues and para-cancer tissues in plateau area using RRBS technology,and methylation differential regions and genes were screened out and their distribution was understood.2.Rna-seq was used to analyze the transcriptome of the same tissue and screen out differentially expressed genes.3.By comprehensive analysis of methylated differential genes and differentially expressed genes,the influence pathway of GENES regulated by DNA methylation on gastric cancer in plateau area was analyzed.4.TBS technology was used to verify some genes regulated by DNA methylation and screen methylation sites that could be used as markers for the diagnosis and treatment of gastric cancer.Results: 1.By genome-wide methylation sequencing,196 991 hypermethylated differential regions and 43 584 hypomethylated differential regions were screened out,corresponding to 45 374 differential methylated genes.These differential regions were mainly distributed in the promoter region,and most of them were on chromosome 1,2and 19.2.A total of 1 005 genes with high expression and 324 genes with low expression were screened by transcriptional sequencing analysis.3.Comprehensive analysis showed that genes regulated by DNA methylation mainly affect tumor metastasis and cell growth through G protein-coupled receptor-mediated signaling pathway,PI3K-Akt signaling pathway and IL-17 signaling pathway,and amino acid metabolism may be the mediator of DNA methylation regulating gastric cancer progression.4.TBS test confirmed that CNR1 gene and FOXP2 gene were differential methylated genes,and part of their methylation sites were potential diagnostic markers for gastric cancer.Conclusion: Through genome-wide methylation sequencing and transcriptome analysis,this study revealed partial methylation characteristics of gastric cancer in plateau area,and found many differentially methylated genes and differentially expressed genes.Through the functional analysis of these genes,it provides a lot of basis for the study of pathogenesis of gastric cancer in plateau area.Through TBS detection,cnr1 and foxp2 genes were confirmed as differential methylation genes,and their related methylation sites are potential diagnostic markers for gastric cancer. |
PDF Full Text Request