Neurosurgical Department, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China.
Obstetrics & Gynecology Department, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China.
Genomics. 2020 Sep;112(5):2990-3002. doi: 10.1016/j.ygeno.2020.05.016. Epub 2020 May 21.
Gliomas account for 75% of the primary malignant brain tumors and a majority of lower-grade gliomas (LGG) inevitably develop into glioblastoma. The dysregulation of lncRNAs play a crucial role in LGG. In the present study, we first screened out six differentially expressed lncRNAs (AC021739.2, AL031722.1, AL354740.1, FGD5-AS1, LINC00844, and NEAT1) based on TCGA and GTEx RNA-seq databases. LncRNA prognostic signature was then established by Kaplan-Meier and multivariate Cox proportional hazards regression, with its predictive value validated by time-dependent receiver operating characteristic (ROC) curves. After lncRNA-miRNA-mRNA regulatory networks were established by Cytoscape 3.7.2, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, with results enriched in various malignancy-related functions and pathways. Finally, six putative drugs (irinotecan, camptothecin, mitoxantrone, azacitidine, mestranol, and enilconazole) were predicted by Connectivity Map. In conclusion, we identified a 6-lncRNA prognostic signature with its ceRNA networks, and six candidate drugs against LGG.
神经胶质瘤占原发性脑恶性肿瘤的 75%，大多数低级别神经胶质瘤（LGG）不可避免地会发展成胶质母细胞瘤。lncRNAs 的失调在 LGG 中起着至关重要的作用。在本研究中，我们首先基于 TCGA 和 GTEx RNA-seq 数据库筛选出六个差异表达的 lncRNA（AC021739.2、AL031722.1、AL354740.1、FGD5-AS1、LINC00844 和 NEAT1）。然后通过 Kaplan-Meier 和多变量 Cox 比例风险回归建立 lncRNA 预后特征，并通过时间依赖性接收器操作特征（ROC）曲线验证其预测价值。通过 Cytoscape 3.7.2 建立 lncRNA-miRNA-mRNA 调控网络后，进行基因肿瘤学（GO）和京都基因与基因组百科全书（KEGG）分析，结果富集于各种恶性相关功能和途径。最后，通过连接图谱预测了六种潜在药物（伊立替康、喜树碱、米托蒽醌、阿扎胞苷、雌三醇和烯菌灵）。总之，我们确定了一个具有 ceRNA 网络的 6-lncRNA 预后特征和六种针对 LGG 的候选药物。
