Coregulatory effects of multiple histone modifications in key ferroptosis-related genes for lung adenocarcinoma.

Aim: The present study was designed to investigate the coregulatory effects of multiple histone modifications (HMs) on gene expression in lung adenocarcinoma (LUAD). Materials & methods: Ten histones for LUAD were analyzed using ChIP-seq and RNA-seq data. An innovative computational method is proposed to quantify the coregulatory effects of multiple HMs on gene expression to identify strong coregulatory genes and regions. This method was applied to explore the coregulatory mechanisms of key ferroptosis-related genes in LUAD. Results: Nine strong coregulatory regions were identified for six ferroptosis-related genes with diverse coregulatory patterns (CA9, PGD, CDKN2A, PML, OTUB1 and NFE2L2). Conclusion: This quantitative method could be used to identify important HM coregulatory genes and regions that may be epigenetic regulatory targets in cancers.

Potential biomarkers: The hypomethylation of cg18949415 and cg22193385 sites in colon adenocarcinoma.

Overall cancer hypomethylation had been identified in the past, but it is not clear exactly which hypomethylation site is the more important for the occurrence of cancer. To identify key hypomethylation sites, we studied the effect of hypomethylation in twelve regions on gene expression in colon adenocarcinoma (COAD). The key DNA methylation sites of cg18949415, cg22193385 and important genes of C6orf223, KRT7 were found by constructing a prognostic model, survival analysis and random combination prediction a series of in-depth systematic calculations and analyses, and the results were validated by GEO database, immune microenvironment, drug and functional enrichment analysis. Based on the expression values of C6orf223, KRT7 genes and the DNA methylation values of cg18949415, cg22193385 sites, the least diversity increment algorithm were used to predict COAD and normal sample. The 100 % reliability and 97.12 % correctness of predicting tumor samples were obtained in jackknife test. Moreover, we found that C6orf223 gene, cg18949415 site play a more important role than KRT7 gene, cg22193385 site in COAD. In addition, we investigate the impact of key methylation sites on three-dimensional chromatin structure. Our results will be help for experimental studies and may be an epigenetic biomarker for COAD.

The prediction of tumor and normal tissues based on the DNA methylation values of ten key sites.

Abnormal DNA methylation can alter the gene expression to promote or inhibit tumorigenesis in colon adenocarcinoma (COAD). However, the finding important genes and key sites of abnormal DNA methylation which result in the occurrence of COAD is still an eventful task. Here, we studied the effects of DNA methylation in the 12 types of genomic features on the changes of gene expression in COAD, the 10 important COAD-related genes and the key abnormal DNA methylation sites were identified. The effects of important genes on the prognosis were verified by survival analysis. Moreover, it was shown that the important genes were participated in cancer pathways and were hub genes in a co-expression network. Based on the DNA methylation levels in the ten sites, the least diversity increment algorithm for predicting tumor tissues and normal tissues in seventeen cancer types are proposed. The better results are obtained in jackknife test. For example, the predictive accuracies are 94.17 %, 91.28 %, 89.04 % and 88.89 %, respectively, for COAD, rectum adenocarcinoma, pancreatic adenocarcinoma and cholangiocarcinoma. Finally, by computing enrichment score of infiltrating immunocytes and the activity of immune pathways, we found that the genes are highly correlated with immune microenvironment.