Development of a 3 RNA Binding Protein Signature for Predicting Prognosis and Treatment Response for Glioblastoma Multiforme.
Development of a 3 RNA Binding Protein Signature for Predicting Prognosis and Treatment Response for Glioblastoma Multiforme.
复制标题
DOI：
10.3389/fgene.2021.768930
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Long Y
中科院分区：
文献类型：
--
作者：
Sun R;Pan Y;Mu L;Ma Y;Shen H;Long Y
目的：多形性胶质母细胞瘤（GBM）是最常见的脑恶性肿瘤。它受多种基因调控，GBM患者生存率低，治疗效果不理想。RNA结合蛋白（RBP）的不规则调节与多种恶性肿瘤有关，并与肿瘤的发生、发展有关。因此，有必要建立一个稳定的，多RBP签名起源模型GBM预后和治疗反应预测。 研究方法：基于来自癌症基因组图谱（TCGA）和基因型-组织表达程序（GTEx）数据集的GBM和正常脑组织的RBP数据，筛选出差异表达的RBP（DERBPs）。对DERBPs进行基因本体论和京都基因和基因组百科全书分析，然后分析蛋白质-蛋白质相互作用网络。通过单变量和多变量考克斯回归对DERBPs进行生存分析。然后，根据各种生存相关RBP中的基因特征建立风险评分模型，并通过Kaplan-Meier分析和log-rank检验评估其预后和预测价值。应用基于中枢RBP特征的列线图来估计GBM患者的存活率。Western blot检测蛋白质的表达。 结果：BICC 1、GNL 3L和KHDRBS 2被认为是乳腺癌相关的中心RBP，然后被应用于构建预后模型。高风险评分的GBM患者的生存结果较差。TCGA和中国胶质瘤基因组图谱（CGGA）队列的时间依赖性ROC曲线下面积分别为0.723和0.707，表明预后模型良好。高危组接受放疗或替莫唑胺化疗的生存期短于低危组。列线图对GBM有很强的区分能力，Western blot实验表明3种RBP蛋白在GBM细胞中有不同的表达。 结论：确定的3个中心RBP衍生的风险评分在预测GBM预后和治疗反应中是有效的，并且对GBM患者的治疗有益。
Purpose: Glioblastoma multiforme (GBM) is the most widely occurring brain malignancy. It is modulated by a variety of genes, and patients with GBM have a low survival ratio and an unsatisfactory treatment effect. The irregular regulation of RNA binding proteins (RBPs) is implicated in several malignant neoplasms and reported to exhibit an association with the occurrence and development of carcinoma. Thus, it is necessary to build a stable, multi-RBPs signature-originated model for GBM prognosis and treatment response prediction. Methods: Differentially expressed RBPs (DERBPs) were screened out based on the RBPs data of GBM and normal brain tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx) datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses on DERBPs were performed, followed by an analysis of the Protein-Protein Interaction network. Survival analysis of the DERBPs was conducted by univariate and multivariate Cox regression. Then, a risk score model was created on the basis of the gene signatures in various survival-associated RBPs, and its prognostic and predictive values were evaluated through Kaplan-Meier analysis and log-rank test. A nomogram on the basis of the hub RBPs signature was applied to estimate GBM patients’ survival rates. Moreover, western blot was for the detection of the proteins. Results: BICC1, GNL3L, and KHDRBS2 were considered as prognosis-associated hub RBPs and then were applied in the construction of a prognostic model. Poor survival results appeared in GBM patients with a high-risk score. The area under the time-dependent ROC curve of the prognostic model was 0.723 in TCGA and 0.707 in Chinese Glioma Genome Atlas (CGGA) cohorts, indicating a good prognostic model. What was more, the survival duration of the high-risk group receiving radiotherapy or temozolomide chemotherapy was shorter than that of the low-risk group. The nomogram showed a great discriminating capacity for GBM, and western blot experiments demonstrated that the proteins of these 3 RBPs had different expressions in GBM cells. Conclusion: The identified 3 hub RBPs-derived risk score is effective in the prediction of GBM prognosis and treatment response, and benefits to the treatment of GBM patients.
登录
查看更多内容
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
1.1
作者：
Davis ME
通讯作者：
Davis ME
影响因子：
--
作者：
Gui H;Gong Q;Jiang J;Liu M;Li H
通讯作者：
Li H
影响因子：
2.7
作者：
Li, Wei;Li, Na;You, Chongge
通讯作者：
You, Chongge
影响因子：
7.5
作者：
Luo, Kui;Zhuang, Kai
通讯作者：
Zhuang, Kai