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膀胱癌中具有预后价值的长非编码 RNA 与拷贝数变异的综合分析。

Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer.

机构信息

Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China.

Department of Medical Record Management Section, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

出版信息

J Zhejiang Univ Sci B. 2021 Aug 15;22(8):664-681. doi: 10.1631/jzus.B2000494.

Abstract

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely -, , , ,and ,and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus (GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.

摘要

拷贝数变异(CNVs)可影响长链非编码 RNA(lncRNA)的功能,是一些恶性肿瘤中可见的重要遗传改变。我们分析了具有 CNV 的 lncRNA,以探讨 lncRNA 与膀胱癌(BLCA)预后之间的关系。对 408 例 BLCA 患者的信使 RNA(mRNA)表达水平、DNA 甲基化和 DNA 拷贝数数据进行了综合生物信息学分析。通过聚类分析获得不同的亚型和差异表达的 lncRNA 和编码基因。进行加权基因共表达网络分析(WGCNA)以鉴定共表达基因和 lncRNA 模块。使用 Kaplan-Meier 生存曲线评估与 CNV 相关的 lncRNA 数据及其对癌症预后的影响。多组学整合分析揭示了 5 个具有 CNV 的预后 lncRNA,即、、、、和,确定了与 BLCA 总生存率相关的风险评分特征。此外,在另一个独立的基因表达综合数据库(GEO)数据集 GSE31684 中的验证结果与这些结果一致。京都基因与基因组百科全书(KEGG)富集分析显示,高风险评分模式中富含丝裂原激活蛋白激酶(MAPK)信号通路、粘着斑通路和 Janus 激酶-信号转导和转录激活因子(JAK-STAT)信号通路,表明这些通路的失衡与肿瘤的发展密切相关。我们通过分析 lncRNA 和 CNV 的表达谱揭示了与预后相关的 lncRNA,它们可以作为 BLCA 的预后生物标志物。

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