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鉴定肾透明细胞癌中具有预后意义的染色质重塑基因。

Identification of prognostic chromatin-remodeling genes in clear cell renal cell carcinoma.

机构信息

Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.

Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.

出版信息

Aging (Albany NY). 2020 Nov 20;12(24):25614-25642. doi: 10.18632/aging.104170.

DOI:10.18632/aging.104170
PMID:33232269
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7803503/
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.

摘要

本研究旨在探讨染色质重塑基因对透明细胞肾细胞癌（ccRCC）患者预后的影响。在 TCGA-KIRC 患者中，根据 86 个染色质重塑基因建立了两个亚组。随机森林算法用于特征选择，以鉴定 BPTF、SIN3A 和 CNOT1 为具有良好预后价值的 ccRCC 特征性染色质重塑因子。YY1 被表明是与 BPTF、SIN3A 和 CNOT1 高度相关的基因的转录因子。功能注释表明，BPTF、SIN3A、CNOT1 和 YY1 均参与泛素介导的蛋白水解过程，通路中五种相关 E3 泛素连接酶的高表达表明预后良好。蛋白质网络分析表明 BPTF 对 YY1 具有靶向调节作用。来自国际癌症基因组联盟（ICGC）的另一个独立数据集与 TCGA 的结果具有很强的一致性。总之，我们证明了 BPTF、SIN3A 和 CNOT1 是预测 ccRCC 患者生存良好的新型预后因素。我们预测，染色质重塑基因 BPTF 和 SIN3A 的良好预后价值与 YY1 的调节有关，YY1 调节 E3 泛素连接酶，以进一步降解 ccRCC 中的癌蛋白。

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