研究动态
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一个新的模型,整合染色质调节因子,用于儿童肾母细胞瘤的风险分层、预后预测和微环境特征的研究。

A novel model incorporating chromatin regulatory factors for risk stratification, prognosis prediction, and characterization of the microenvironment in Wilms tumor.

发表日期:2023 Aug 14
作者: Xiaodong Zhao, Xiaobin Chu, Lei Song, Weichun Tang
来源: Epigenetics & Chromatin

摘要:

威尔姆斯瘤,也被称为肾母细胞瘤,是一种儿童最常见的恶性肾肿瘤,可能受到转录和表观遗传机制的调控和影响。染色质调控因子在表观遗传调控中发挥关键作用。本研究旨在探讨CRs在肾母细胞瘤发生中的参与。通过从TARGET数据库下载肾母细胞瘤样本的RNA测序数据和临床信息。使用Limma包对肿瘤组和对照组的基因差异表达进行分析。使用Venn图对差异基因和CRs进行交集分析,并使用clusterProfiler包对差异基因进行基因本体论和KEGG富集分析。使用LASSO和Cox分析构建CR相关风险模型,并根据临床参数进行评估。使用受试者工作特征曲线评估风险模型的诊断性能。此外,我们还使用单样品基因集富集分析算法进行免疫细胞浸润分析。最后,为了确认人肾母细胞瘤细胞系中关键基因的转录组表达情况,采用定量实时聚合酶链式反应(qPCR)。 通过对肾母细胞瘤的分析获得了15个关键CRs,然后使用肾母细胞瘤的转录组数据构建了基于13个重要CRs的风险模型。使用该风险模型,将小儿肾母细胞瘤患者根据个体风险评分分为高风险组和低风险组。CRs的风险评分可以预测小儿肾母细胞瘤的不良预后,并且该基因簇与肾母细胞瘤的各种免疫特征密切相关。此外,与HEK293 T细胞系相比,肾母细胞瘤细胞系显示出更高的预后基因(VRK1、ARNTL、RIT1、PRDM6和TSPY1)表达水平。 通过CRs衍生的风险特征在预测儿童肾母细胞瘤的预后和指导临床分类和干预策略方面具有重要意义。© 2023 John Wiley & Sons Ltd.
Wilms tumor, also known as nephroblastoma, a pediatric most-frequent malignant-kidney tumor, may be regulated and influenced by transcriptional and epigenetic mechanisms. Chromatin regulatory factors (CRs) play key roles in epigenetic regulation. The present study aimed to explore the involvement of CRs in the development of nephroblastoma.RNA-sequencing and clinical information of nephroblastoma samples were obtained by downloading data from the TARGET database. The Limma package was utilized to perform differential expression analysis of genes (DEGs) between the tumor group and the control group. A Venn map was used for intersection of differential genes and CRs and to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs using the clusterProfiler package. LASSO and Cox analyses were used to construct CR-related risk models and were evaluated based on clinical parameters. A receiver operating characteristic curve was employed to assess the diagnostic performance of risk model. Furthermore, we used a single-sample gene set enrichment analysis algorithm for immune cell infiltration analysis. Finally, to confirm the transcriptome expression of pivotal genes in human nephroblastoma cell lines, a quantitative real-time PCR was employed.Fifteen key CRs were obtained through analysis in nephroblastoma and then the risk model based on 13 important CRs was constructed using the transcriptome data of nephroblastoma. Using the risk model, pediatric nephroblastoma patients were stratified into high- and low-risk groups based on their individual risk scores. The risk score of CRs can predict adverse outcomes in pediatric nephroblastoma, and this gene cluster is closely related to various immunity characteristics of nephroblastoma. Moreover, the nephroblastoma cell line exhibited higher expression levels of prognostic genes (VRK1, ARNTL, RIT1, PRDM6, and TSPY1) compared to the HEK293 T cell line.The risk characteristics derived from CRs have tremendous significance in predicting prognosis and guiding clinical classification and intervention strategies for pediatric nephroblastoma.© 2023 John Wiley & Sons Ltd.