Dataset Information

Genome-wide analysis of the hypoxia-related DNA methylation-driven genes in lung adenocarcinoma progression.

ABSTRACT: Lung adenocarcinoma (LUAD) is a common type of lung cancer with high incidence and poor prognosis. Hypoxia and DNA methylation play important regulatory roles in cancer progression. The purpose of the present study was to explore the relationship between hypoxia and DNA methylation, and to identify key genes for hypoxia-regulated LUAD progression. Hypoxia score (HS) was calculated using the GSVA algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) analysis were performed using clusterProfile package, STRING database and Cytoscape software. Kaplan-Meier curves of overall survival (OS) and disease-free survival (DFS) were drawn using R software. Smoking status and cancer stages were significantly associated with LUAD hypoxia, and hypoxia is a poor prognostic factor for LUAD. Compared with HS-low group, 1803 aberrantly methylated DEGs were identified in HS-high group. KEGG analysis showed that the 1803 genes were enriched in the metabolic pathways associated with hypoxia stress, angiogenesis and cancer progression. FAM20C, MYLIP and COL7A1 were identified as the hypoxia-related key genes in LUAD progression, which were regulated by DNA methylation. Hypoxia in LUAD tumor cells led to changes in DNA methylation patterns. In-depth study of the relationship between hypoxia and DNA methylation is helpful to elucidate the mechanism of tumorigenesis, and provides new ideas for LUAD treatment.

SUBMITTER: Li H

PROVIDER: S-EPMC7033312 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Genome-wide analysis of the hypoxia-related DNA methylation-driven genes in lung adenocarcinoma progression.

Li Hongxia H Tong Li L Tao Hong H Liu Zhe Z

Bioscience reports 20200201 2

Lung adenocarcinoma (LUAD) is a common type of lung cancer with high incidence and poor prognosis. Hypoxia and DNA methylation play important regulatory roles in cancer progression. The purpose of the present study was to explore the relationship between hypoxia and DNA methylation, and to identify key genes for hypoxia-regulated LUAD progression. Hypoxia score (HS) was calculated using the GSVA algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and ...[more]

PMID: 32031203

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Project description:BackgroundProstate cancer (PCa) remains the second leading cause of deaths due to cancer in the United States in men. The aim of this study was to perform an integrative epigenetic analysis of prostate adenocarcinoma to explore the epigenetic abnormalities involved in the development and progression of prostate adenocarcinoma. The key DNA methylation-driven genes were also identified.MethodsMethylation and RNA-seq data were downloaded for The Cancer Genome Atlas (TCGA). Methylation and gene expression data from TCGA were incorporated and analyzed using MethylMix package. Methylation data from the Gene Expression Omnibus (GEO) were assessed by R package limma to obtain differentially methylated genes. Pathway analysis was performed on genes identified by MethylMix criteria using ConsensusPathDB. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also applied for the identification of pathways in which DNA methylation-driven genes significantly enriched. The protein-protein interaction (PPI) network and module analysis in Cytoscape software were used to find the hub genes. Two methylation profile (GSE112047 and GSE76938) datasets were utilized to validate screened hub genes. Immunohistochemistry of these hub genes were evaluated by the Human Protein Atlas.ResultsA total of 553 samples in TCGA database, 32 samples in GSE112047 and 136 samples in GSE76938 were included in this study. There were a total of 266 differentially methylated genes were identified by MethylMix. Plus, a total of 369 differentially methylated genes and 594 differentially methylated genes were identified by the R package limma in GSE112047 and GSE76938, respectively. GO term enrichment analysis suggested that DNA methylation-driven genes significantly enriched in oxidation-reduction process, extracellular exosome, electron carrier activity, response to reactive oxygen species, and aldehyde dehydrogenase [NAD(P)+] activity. KEGG pathway analysis found DNA methylation-driven genes significantly enriched in five pathways including drug metabolism-cytochrome P450, phenylalanine metabolism, histidine metabolism, glutathione metabolism, and tyrosine metabolism. The validated hub genes were MAOB and RTP4.ConclusionsMethylated hub genes, including MAOB and RTP4, can be regarded as novel biomarkers for accurate PCa diagnosis and treatment. Further studies are needed to draw more attention to the roles of these hub genes in the occurrence and development of PCa.

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Dataset Information

Genome-wide analysis of the hypoxia-related DNA methylation-driven genes in lung adenocarcinoma progression.

Publications

Genome-wide analysis of the hypoxia-related DNA methylation-driven genes in lung adenocarcinoma progression.

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