Differential Methylated Probes At Pan-cancer Level And Association Analysis With Gene Expression,Mutational Signatures And Immune Signatures

DNA methylation as an important epigenetic modification,more and more studies have shown that it is associated with many diseases,especially in cancer.DNA methylation modification is reversible and can dynamically regulate the expression of key genes,which may contribute to the treatment of diseases and become a drug gold mine for treating tumor diseases in the near future.In the whole life of the human body,human cells have the possibility of somatic mutations.Mutational signatures play an important role in the development and progression of cancer.Moreover,mutational signatures are diverse in the development of cancer.Therefore,the diversity of mutational signatures may have potential implications for understanding the etiology,prevention,diagnosis,and treatment of cancer.The immune system can help us fight the threat of diseases.As people gradually understanding the details of the way that the body’s immune system works and the in-depth study of the mechanisms of tumor escaping immune monitoring,researchers can intervene and optimize the immune response to achieve the goal of treating various diseases such as cancer in the future.Most studies on the relationship between DNA methylation and cancer have focused on the study of specific genes in individual tumors or in individual tumors,but there has been little research at the level of pan-cancer.Therefore,we studied DNA methylation at the level of pan-cancer including COAD(Colon adenocarcinoma),LUAD(Lung adenocarcinoma),THCA(Thyroid carcinoma),LIHC(Liver hepatocellular carcinoma),HNSC(Head and neck squamous cell carcinoma),KIRP(Kidney renal papillary cell carcinoma),PRAD(Prostate adenocarcinoma),BRCA_ERp(Breast invasive carcinoma(ER positive)),and KIRC(Kidney renal clear Cell carcinoma).DMPs(differential methylated probes)were found in 9 tumors,and verified in colon adenocarcinoma.At the same time,we combined RNA-Seq data to correlate DMPs with gene expression(both in-cis and in-trans).We described the distribution of the location in relation to genes and CpG islands of DMPs and DMPs that were significantly associated with gene expression,and performed position enrichment and KEGG enrichment analysis.Further more,we conducted a association analysis among the average level of hyper-DMPs or hypo-DMPs,mutational signature,and immune signature,and found some significant correlations.By comparing the similarities and differences between the nine tumors,our study provides an interface between DNA methylation,mutational signature,immune signature,and gene expression,and provides thoughts and abundant materials in further research into the mechanisms of cancer occurrence and development at the pan-cancer level or in specific tumors.