Correlation Analysis Between Gene Differential Expression And DNA Methylation In Lung Squamous Cell Carcinoma

The differential expression of genes is often regulated by DNA methylation.The correlation analysis between DNA methylation and differential expression of genes is helpful to infer the regulation mechanism of gene expression,especially genes related to diseases.In this paper,using the RNA-Seq data of lung squamous cell carcinoma(LUSC)from the TCGA database,combined the DESeq2 package with analysis of variance,the differentially expressed gene sets of up-regulated and down-regulated associated with LUSC were constructed.By integrating the DNA methylation data of LUSC from the TCGA database,the DNA methylation values of CpG sites were obtained in the 6 functional regions of the up-regulated and down-regulated genes.The comparison and analysis between LUSC and normal tissues showed that the DNA methylation level distribution of each functional region was consistent in up and down-regulated genes.But the DNA methylation level distribution between six functional regions was different.For the up and down-regulated genes,the pearson correlation coefficient(PCC)between DNA methylation of each CpG site and gene expression level was calculated.The results showed that the average PCC values of the up and down-regulated genes were 0.114 and 0.129 respectively.Although the overall PCC values were low,there are some CpG sites whose DNA methylation are strongly related to gene expression.The largest PCC value reached 0.777 and the PCC values of 57 CpG sites are over 0.6.Based on the DNA methylation data from 367 LUSC samples and 7 normal samples,the CpG site sets with differential DNA methylation between LUSC and normal tissues were obtained for each functional region of up and down-regulated genes by using Limma package.The analysis found the densities of differential DNA methylation site exist obvious different between functional regions.And the density in the first exon region is the largest for the up and down-regulated genes.For the differential DNA methylation sites of up and down-regulated genes,48 genes and 106 CpG sites with significant correlation were extracted by analyzing the correlation between gene expression and DNA methylation.Survival analysis showed that 24 genes of them affect the prognosis of patients with LUSC.Furthermore,we calculated the correlation between changes of gene expression and changes of DNA methylation for 48 genes and 106 sites,and found that the expression differences of15 genes were significantly related to DNA methylation differences of its 23 CpG sites.The prediction results showed that these sites and genes can effectively identify LUSC and normal samples.As a result,we think that these sites and genes can be considered as key genes and key DNA methylation sites in LUSC.