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通过生物信息学分析鉴定胶质母细胞瘤中的生物标志物和竞争性内源RNA网络并评估潜在预后价值

Identification of biomarkers and ceRNA network in glioblastoma through bioinformatic analysis and evaluation of potential prognostic values.

作者信息

Hong Fan, Gong Zhenyu, Zhang Xu, Ma Peipei, Yin Yongxiang, Wang Hongxiang

机构信息

Department of Neurosurgery, Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China.

Department of Neurosurgery, Changzheng Hospital, Naval Medical University, Shanghai, China.

出版信息

Ann Transl Med. 2021 Oct;9(20):1561. doi: 10.21037/atm-21-4925.

Abstract

BACKGROUND

Glioblastoma (GBM) is one of the most common and malignant primary brain tumors in adults, with high mortality rates and limited treatment. Based on bioinformatic analyses, this study aimed to identify biomarkers and relevant molecular pathways that may serve as potential targets for the treatment of GBM.

METHODS

Expression profiles were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database; nine GBM samples and three normal samples were extracted from the GSE104267 dataset. Differentially-expressed messenger RNA (mRNA) and long non-coding RNA (lncRNA) were screened from the preprocessed dataset. The clusterProfiler package in R was used to perform a biological process (BP) analysis of gene ontology (GO), and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed separately in upregulated and downregulated groups. A competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Based on data downloaded from The Cancer Genome Atlas (TCGA), Kaplan-Meier (K-M) survival curves were established. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to evaluate IL10RB antisense RNA 1 (IL10RB-AS1) expression in GBM tissue compared with that in normal brain tissue.

RESULTS

A total of 253 differentially-expressed genes (DEGs) were obtained. Based on BP and KEGG enrichment annotation analyses, 11 lncRNA-related pathways were identified through function prediction analysis. A competing endogenous RNA (ceRNA) subnetwork, including 21 nodes and 29 regulatory pairs, was then constructed. Based on the clinical data of GBM in TCGA, one survival-related DEG, IL10RB-AS1, was identified using the log-rank statistical test. K-M survival curves of IL10RB-AS1 and expression levels of IL10RB-AS1 in both GBM and normal brain tissue were obtained.

CONCLUSIONS

Through the combination of bioinformatic analyses, one survival-related differentially-expressed lncRNA, IL10RB-AS1, was identified. This, along with several related signaling pathways and ceRNA systems that were elucidated in GBM have potential prognostic value and might offer new possibilities for the treatment of GBM.

摘要

背景

胶质母细胞瘤(GBM)是成人中最常见且恶性程度最高的原发性脑肿瘤之一,死亡率高且治疗手段有限。基于生物信息学分析,本研究旨在识别可能作为GBM治疗潜在靶点的生物标志物和相关分子通路。

方法

从美国国立生物技术信息中心(NCBI)的基因表达综合数据库(GEO)下载表达谱;从GSE104267数据集中提取9个GBM样本和3个正常样本。从预处理数据集中筛选差异表达的信使核糖核酸(mRNA)和长链非编码核糖核酸(lncRNA)。使用R语言中的clusterProfiler软件包对基因本体(GO)进行生物学过程(BP)分析,并分别对上调和下调组进行京都基因与基因组百科全书(KEGG)通路富集分析。使用Cytoscape构建竞争性内源RNA(ceRNA)网络。基于从癌症基因组图谱(TCGA)下载的数据,绘制Kaplan-Meier(K-M)生存曲线。进行实时定量逆转录聚合酶链反应(qRT-PCR)以评估GBM组织中IL10RB反义RNA 1(IL10RB-AS1)与正常脑组织中的表达情况。

结果

共获得253个差异表达基因(DEG)。基于BP和KEGG富集注释分析,通过功能预测分析鉴定出11条lncRNA相关通路。随后构建了一个包含21个节点和29个调控对的竞争性内源RNA(ceRNA)子网。基于TCGA中GBM的临床数据,使用对数秩统计检验鉴定出一个与生存相关的DEG,即IL10RB-AS1。获得了IL10RB-AS1的K-M生存曲线以及其在GBM和正常脑组织中的表达水平。

结论

通过生物信息学分析相结合,鉴定出一个与生存相关的差异表达lncRNA,即IL10RB-AS1。这与在GBM中阐明的几种相关信号通路和ceRNA系统具有潜在的预后价值,并可能为GBM的治疗提供新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1402/8576643/a91ac4547a1a/atm-09-20-1561-f1.jpg

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