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- Title
Identification and Comprehensive Validation of a DNA Methylation-Driven Gene-Based Prognostic Model for Clear Cell Renal Cell Carcinoma.
- Authors
Zhang, Di; Wang, Yicun; Hu, Xiaopeng
- Abstract
Clear cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy in adults with generally poor prognosis. This study aimed to establish a DNA methylation-driven gene-based prognostic model for ccRCC. We collected DNA methylation and gene expression profiles of over 1500 ccRCC samples from The Cancer Genome Atlas (TCGA) dataset, four Gene Expression Omnibus (GEO) datasets, the Genotype-Tissue Expression (GTEx) dataset, and cancer cell lines from Cancer Cell Line Encyclopedia database and performed comprehensive bioinformatics analysis. As a result, a total of 31 differentially expressed methylation-driven genes (DEMDGs) were identified. After univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, four (NFE2L3, HHLA2, IFI16, and ZNF582) were finally selected to construct a risk score prognostic model. The high-risk group demonstrated significantly poor prognosis than the low-risk group did in TCGA training (hazard ratio [HR] = 3.533, p < 0.001), TCGA internal, and GEO external validation datasets. Furthermore, the nomogram, including the prognostic model and clinical factors, showed promising prognostic value (HR = 5.756, p < 0.001, and area under the curve at 1 year = 0.856). In addition, the model was found to be significantly associated with drug sensitivity of eight targeted agents. These findings provided a novel and reliable four DEMDG-based prognostic model for ccRCC.
- Subjects
RENAL cell carcinoma; GENE expression profiling; DNA; DNA methylation; GENE expression; PROGNOSTIC models
- Publication
DNA & Cell Biology, 2020, Vol 39, Issue 10, p1799
- ISSN
1044-5498
- Publication type
Article
- DOI
10.1089/dna.2020.5601