Unveiling new interdependencies between significant DNA methylation sites, gene expression profiles and glioma patients survival
| Autor: | Bartosz Wojtas, Jacek Koronacki, Michal J. Dabrowski, Jan Komorowski, Klev Diamanti, Karolina Stepniak, Magdalena A. Mozolewska, Bozena Kaminska, Paweł Teisseyre, Michał Dramiński |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell- och molekylärbiologi Molecular Conformation lcsh:Medicine RE1-silencing transcription factor Kaplan-Meier Estimate Biology Article Epigenesis Genetic 03 medical and health sciences Structure-Activity Relationship Glioma Gene expression medicine Humans lcsh:Science Promoter Regions Genetic Transcription factor Neoplasm Staging Cancer och onkologi Multidisciplinary Gene Expression Profiling lcsh:R Computational Biology Molecular Sequence Annotation Methylation DNA DNA Methylation medicine.disease Prognosis Gene expression profiling 030104 developmental biology CpG site Cancer and Oncology DNA methylation Mutation Cancer research biology.protein lcsh:Q CpG Islands Neoplasm Grading Transcriptome Monte Carlo Method Cell and Molecular Biology |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| Popis: | In order to find clinically useful prognostic markers for glioma patients’ survival, we employed Monte Carlo Feature Selection and Interdependencies Discovery (MCFS-ID) algorithm on DNA methylation (HumanMethylation450 platform) and RNA-seq datasets from The Cancer Genome Atlas (TCGA) for 88 patients observed until death. The input features were ranked according to their importance in predicting patients’ longer (400+ days) or shorter (≤400 days) survival without prior classification of the patients. Interestingly, out of the 65 most important features found, 63 are methylation sites, and only two mRNAs. Moreover, 61 out of the 63 methylation sites are among those detected by the 450 k array technology, while being absent in the HumanMethylation27. The most important methylation feature (cg15072976) overlaps with the RE1 Silencing Transcription Factor (REST) binding site, and was confirmed to intersect with the REST binding motif in human U87 glioma cells. Six additional methylation sites from the top 63 overlap with REST sites. We found that the methylation status of the cg15072976 site affects transcription factor binding in U87 cells in gel shift assay. The cg15072976 methylation status discriminates ≤400 and 400+ patients in an independent dataset from TCGA and shows positive association with survival time as evidenced by Kaplan-Meier plots. |
| Databáze: | OpenAIRE |
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