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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Integrated Bioinformatics Analysis of DNA Methylation Biomarkers in Thyroid Cancer Based on TCGA Database
Lifeng Zhao1, Yuanyuan Jia2, Ying Liu2
1Department of Endocrinology, Tianjin First Center Hospital, No. 24, Fu-Kang Road, Nankai District, Tianjin, 300192, China. lifeng_zhao0203@yeah.net.
Abstract:
Previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes in thyroid cancer (TC), but these results of individual genes are far from enough. In this work, we aimed to investigate the onset and pattern of methylation changes during the progression of TC by informatics analysis. We downloaded the DNA methylation and RNA sequencing datasets from The Cancer Genome Atlas focusing on TC. Abnormally methylated differentially expressed genes (DEGs) were sorted and pathways were analyzed. The KEGG and GO were then used to perform enrichment and functional analysis of identified pathways and genes. Gene-drug interaction network and human protein atlas were applied to obtain feature DNA methylation biomarkers. In total, we identified 2170 methylation-driven DEGs, including 1054 hypermethylatedlow-expression DEGs and 1116 hypomethylated-high-expression DEGs at the screening step. Further analysis screened total of eight feature DNA methylation biomarkers (RXRG, MET, PDGFRA, FCGR3A, VEGFA, CSF1R, FCGR1A and C1QA). Pathway analysis showed that aberrantly methylated DEGs mainly associated with transcriptional misregulation in cancer, MAPK signaling, and intrinsic apoptotic signaling in TC. Taken together, we have identified novel aberrantly methylated genes and pathways linked to TC, which might serve as novel biomarkers for precision diagnosis and disease treatment.
Insights
This study identifies novel DNA methylation biomarkers and pathways in thyroid cancer (TC) progression. These findings offer potential for improved precision diagnosis and treatment strategies for this disease.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Aberrant promoter methylation is linked to tumor suppressor gene silencing in thyroid cancer (TC).
- Previous studies focused on individual genes, necessitating a broader analysis of methylation changes during TC progression.
Purpose of the Study:
- To investigate the onset and pattern of DNA methylation changes throughout thyroid cancer progression using bioinformatics analysis.
- To identify novel methylation-driven differentially expressed genes (DEGs) and associated pathways as potential biomarkers for TC.
Main Methods:
- Downloaded and analyzed DNA methylation and RNA sequencing data from The Cancer Genome Atlas (TCGA) for TC.
- Identified abnormally methylated DEGs, performed pathway enrichment analysis (KEGG, GO), and constructed gene-drug interaction networks.
- Utilized the Human Protein Atlas to identify feature DNA methylation biomarkers.
Main Results:
- Identified 2170 methylation-driven DEGs (1054 hypermethylated-low-expression, 1116 hypomethylated-high-expression).
- Screened eight feature DNA methylation biomarkers: RXRG, MET, PDGFRA, FCGR3A, VEGFA, CSF1R, FCGR1A, and C1QA.
- Pathway analysis revealed associations with transcriptional misregulation in cancer, MAPK signaling, and intrinsic apoptotic signaling in TC.
Conclusions:
- Novel aberrantly methylated genes and pathways associated with thyroid cancer have been identified.
- These findings suggest potential utility as biomarkers for the precise diagnosis and treatment of TC.
- The study highlights the importance of comprehensive methylation profiling in understanding TC pathogenesis.
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