Association Analysis Of Gene Expression And Methylation To Excavate Potential Tumor Markers Induced By Hepatocellular Carcinoma

BackgroundLiver cancer is one of the most common malignant tumors.The morbidity and mortality rate of liver cancer is high.It is very important to evaluate the prognosis reasonably and to intervene properly.At present,the research reveals that liver cancer is a genetic disease.It is a synergistic process involving multiple oncogenes and anticancer genes.It is a multi-stage and multi-channel synergy that makes the liver cells develop into precancerous lesions,and then develop into the evolution process of liver cancer.Differentially expressed in genes exist in the process of normal hepatocyte changed to precancerous and precancerous changed to hepatocellular carcinoma.Now,Molecular Pathology merges Molecular Hybridization with histomorphology.With the development of immunohistochemistry and molecular biology,the pathology of liver cancer is becoming more and more inseparable with immunology and molecular biology.At present,many genes and their protein products related to liver cancer have been explored.The early discovery of these genes and markers has opened up a new way to study the pathogenesis of liver cancer,which can reveal the growth activity of tumor tissue in the role of invasion and metastasis and guide clinical treatment and prognosis more accurately.ObjectiveAssociation analysis of whole Gene expression profile and methylation spectrum to excavate the prognostic markers driven by Hepatocellular carcinoma.Material and MethodDownload 450 k methylation and RNA-seq data for liver cancer,Matched methylation and RNA-seq in same cancer and paracancerous samples.After standardizing the data,we further screen the genes and methylation genes that have different expression in cancer and paracancerous in every samples.Further we find out the genes that have contrary promoter methylation expression and genes expression,that is,differential up-regulation and differential promoter methylation down-regulation gene(Epigenetically induced,EI)and differential down-regulation of its differential promoter methylation up-regulation gene(Epigenetically suppressed,ES).Further we can calculate the correlation between promoter methylation and expression of EI and ES genes through analysising the function of these genes by enrichment analysis.Screen of genes with significant negative correlation as final EI and ES genes and Integrate human protein interaction networks to construct EI |ES interaction subnet and dig out the key gene in the subnet.Analysis of the function of key genes and the changes of expression in carcinogenesis and progression and their influence on prognosis.Further use of GEO data to verify the relationship between key gene expression and promoter methylation in cancer.Results450 k data of RNA-seq and methylated from 41 pairs of cancer and para-cancerous samples were obtained from the TCGA dataset.We can get 5119 genes from 17937 genes which have different gene expression in cancer and paracancer samples according to the principle of differential screening,Of these genes,4519 genes were up-regulated and 600 genes down-regulated.We can get8853 promoter methylation gene from 17937 promoter methylation gene which have different gene expression in cancer and paracancer samples,Of these genes,3467 genes were up-regulated and 5386 genes down-regulated.There was a negative correlation between DNA promoter methylation and gene expression in normal and cancerous tissues.There were 1177 difference up-regulated and promoter methylation difference down-regulated genes(EI),and 165 difference down-regulated and promoter methylated up-regulated genes(ES).A total of 419 EI genes and 68 ES genes were obtained by further screening for genes with significant negative correlation.Construct EI-ES gene interaction subnet and there are 315 interacting genes,among which the gene with the highest enrichment of EI|ES gene and the FDR of the significant p value less than 0.05 is TIPIN?RBM15B?DUSP28?TRIM31,respectively.There was significant difference in the expression of TIPIN?RBM15B in each stage of cancer,and the difference was statistically significant(P = 0.00228,0.00562,respectively).The expression level of TIPIN?RBM15B showed significant difference in prognosis,and the difference was statistically significant(P = 0.037,0.0064,respectively).The expression in various stage of cancer and prognosis of DUSP28?TRIM31 have no significant difference.ConclusionWe use the GEO dataset GSE2977 to verify that there is a significant difference between the expression of TIPIN?RBM15B and promoter methylation,and that there is mutual exclusion.1? The potential tumor marker induced by liver cancer isTIPIN?RBM15B.2? TIPIN?RBM15B is closely related to the occurrence and development of liver cancer.3? TIPIN ? RBM15 B is closely related to the prognosis of patients with high expression of TIPIN?RBM15B is poor.4? TIPIN?RBM15B have an significant difference between the expression of and promoter methylation,and there is mutual exclusion.