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Identification of DNA methylation-driven genes in esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas.

ABSTRACT: Background:Aberrant DNA methylations are significantly associated with esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the DNA methylation-driven genes in ESCC by integrative bioinformatics analysis. Methods:Data of DNA methylation and transcriptome profiling were downloaded from TCGA database. DNA methylation-driven genes were obtained by methylmix R package. David database and ConsensusPathDB were used to perform gene ontology (GO) analysis and pathway analysis, respectively. Survival R package was used to analyze overall survival analysis of methylation-driven genes. Results:Totally 26 DNA methylation-driven genes were identified by the methylmix, which were enriched in molecular function of DNA binding and transcription factor activity. Then, ABCD1, SLC5A10, SPIN3, ZNF69, and ZNF608 were recognized as significant independent prognostic biomarkers from 26 methylation-driven genes. Additionally, a further integrative survival analysis, which combined methylation and gene expression data, was identified that ABCD1, CCDC8, FBXO17 were significantly associated with patients' survival. Also, multiple aberrant methylation sites were found to be correlated with gene expression. Conclusion:In summary, we studied the DNA methylation-driven genes in ESCC by bioinformatics analysis, offering better understand of molecular mechanisms of ESCC and providing potential biomarkers precision treatment and prognosis detection.

SUBMITTER: Lu T

PROVIDER: S-EPMC6404309 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification of DNA methylation-driven genes in esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas.

Lu Tong T Chen Di D Wang Yuanyong Y Sun Xiao X Li Shicheng S Miao Shuncheng S Wo Yang Y Dong Yanting Y Leng Xiaoliang X Du Wenxing W Jiao Wenjie W

Cancer cell international 20190306

<h4>Background</h4>Aberrant DNA methylations are significantly associated with esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the DNA methylation-driven genes in ESCC by integrative bioinformatics analysis.<h4>Methods</h4>Data of DNA methylation and transcriptome profiling were downloaded from TCGA database. DNA methylation-driven genes were obtained by methylmix R package. David database and ConsensusPathDB were used to perform gene ontology (GO) analysis and ...[more]

PMID: 30886542

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Project description:BackgroundMicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA).MethodsIntegrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients' tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients' clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients' tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student's t test, Pearson Chi-squared test and Kaplan-Meier survival analysis were used in this study.ResultsThirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients' tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) were correlated with overall survival of ESCC patients (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients' tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar.ConclusionThis study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.

Dataset Information

Identification of DNA methylation-driven genes in esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas.

Publications

Identification of DNA methylation-driven genes in esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas.

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