Differentially Expressed Genes And Their Association With DNA Methylation In Lung Squamous Cell Carcinoma

Differentially expressed genes(DEGs)and epigenetic regulation play an important role in the occurrence and progression of cancer.In order to explore the molecular mechanism in lung squamous cell carcinoma(LUSC),firstly,the gene expression profiling data including 502 LUSC samples(named cancer group)and 49 normal samples(named normal group)as well as the matched Methylation 450 K data(370 LUSC samples and 42 normal samples)associated with LUSC were downloaded from TCGA.Using DESeq2 combined with analysis of variance(ANOVA),genes were identified with different expression level within and between sample groups,and five gene sets were established.Secondly,based on the cancer genes confirmed by researches or experiments from COSMIC,DISEASES and CCGD databases,the percentage of cancer genes in each set was calculated.According to oncogenes and tumor suppressor genes(TSG)lists in COSMIC and Nucleic Acids Res databases,the potential oncogene and TSG were obtained by Wayne method.Thirdly,the highly and lowly expressed genes with extremely significant differences between cancer and normal groups were selected for the following research.The distribution of DNA methylation levels of these genes in cancer and normal tissues,and the relationship between gene expression level and DNA methylation level were analyzed.We found the proportion of oncogenes in five gene sets with LUSC were 47.2%,38.7%,61.6%,55.6% and 38.2%,and the proportion of lung cancer genes in each set were 2.3%,0.9%,1.5%,2.2% and 0.9%.It revealed that inter-group differential gene sets filtering by ANOVA contained more cancer and lung cancer genes.Then,72 potential oncogenes and 244 potential TSG were obtained.The results showed the overall DNA methylation level was lower in cancer tissues for up-regulated and down-regulated expression genes than in normal tissues.In addition,the DNA methylation levels in five functional regions of cancer tissues changed significantly.Finally,the correlation analysis showed that the DNA methylation levels of exon and intron regions were slightly more correlated with gene expression positively or negatively regulation.And 4 genes with strong positive correlation and 31 genes with strong negative correlation were found.Above findings is helpful for understanding the molecular mechanism in LUSC in more details.