Research Paper Volume 12, Issue 24 pp 25614—25642
Identification of prognostic chromatin-remodeling genes in clear cell renal cell carcinoma
- 1 Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China
- 2 Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China
- 3 Department of Medical Oncology, Shenyang Fifth People Hospital, Tiexi District, Shenyang 110001, P.R. China
Received: March 24, 2020 Accepted: September 28, 2020 Published: November 20, 2020
https://doi.org/10.18632/aging.104170How to Cite
Abstract
The aim of this study was to investigate the effects of chromatin-remodeling genes on the prognosis of patients with clear cell renal cell carcinoma (ccRCC). In TCGA-KIRC patients, two subgroups based on 86 chromatin-remodeling genes were established. The random forest algorithm was used for feature selection to identify BPTF, SIN3A and CNOT1 as characterized chromatin remodelers in ccRCC with good prognostic value. YY1 was indicated to be a transcription factor of genes highly related to BPTF, SIN3A and CNOT1. Functional annotations indicated that BPTF, SIN3A, CNOT1 and YY1 are all involved in the ubiquitin-mediated proteolysis process and that high expression of any of the five associated E3 ubiquitin ligases found in the pathway suggests a good prognosis. Protein network analysis indicated that BPTF has a targeted regulatory effect on YY1. Another independent dataset from International Cancer Genome Consortium (ICGC) showed a strong consistency with results in TCGA. In conclusion, we demonstrate that BPTF, SIN3A and CNOT1 are novel prognostic factors that predict good survival in ccRCC. We predicted that the good prognostic value of chromatin-remodeling genes BPTF and SIN3A is related to the regulation of YY1 and that YY1 regulates E3 ubiquitin ligases for further degradation of oncoproteins in ccRCC.
Abbreviations
ccRCC: clear cell renal cell carcinoma; TCGA-KIRC: The Cancer Genome Atlas-Kidney Renal Cell Carcinoma; HumanTFDB: Human Transcription Factor Database; FPKM: fragment per kilobase per million; RPKM: reads per kilobase per million; MAF: mutational annotation format; MAD: median absolute deviation; AUC: areas under the curve; GEPIA: Gene Expression Profiling Interactive Analysis; FDR: false discovery rate; CDF: cumulative distribution function; GSEA: gene-set enrichment analysis; KEGG: Kyoto Encyclopedia of Genes and Genomes; OS: overall survival; PFS: progression-free survival; COSMIC: Catalogue of Somatic Mutations in Cancer; GO: Gene Ontology; NURF: nucleosome-remodeling factor; ICGC: International Cancer Genome Consortium.