Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012, China.
Int J Med Sci. 2020 Sep 1;17(16):2427-2439. doi: 10.7150/ijms.49053. eCollection 2020.
Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and "limma" package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all <0.05). Furthermore, we identified elevated TPX2 was strongly correlated with the worse survival rate among 458 samples. Univariate and multivariate cox analysis showed TPX2 may act as an independent factor for prognosis in LUAD ( <0.05). Then pathway enrichment results suggested that TPX2 may facilitate tumorigenesis by participating in several cancer-related signaling pathways in LUAD, especially in Notch signal pathway. TPX2-related lncRNAs and miRNAs are related to the survival of LUAD. 7 lncRNAs, 7 miRNAs and TPX2 may serve as prognostic biomarkers in LUAD.
竞争性内源 RNA（ceRNA）被认为在肿瘤发生中发挥重要作用。本研究的目的是筛选肺腺癌（LUAD）的预后生物标志物。使用 GEO2R 和 R 中的“limma”包，分别从基因表达综合数据库（GEO）和癌症基因组图谱数据库（TCGA）中收集共同差异表达基因（DEGs）。使用功能富集和蛋白质-蛋白质相互作用（PPI）网络对重叠 DEGs 进行分析，以发现显著的候选基因。通过综合分析，构建了一个 mRNA 介导的 ceRNA 网络。使用 Kaplan-Meier 分析评估生存率。统计分析用于进一步确定研究基因的预后。通过整合 GSE32863 和 TCGA 数据库分析，共鉴定出 886 个重叠的 DEGs，包括 279 个上调基因和 607 个下调基因。考虑到候选基因 PPI 中的最高术语，我们鉴定出 TPX2，其富集于细胞分裂信号通路。此外，预测了 35 个差异表达 miRNA（DEmiRNA）靶向 TPX2，仅鉴定出 7 个 DEmiRNA 是 LUAD 的预后生物标志物。然后，预测 30 个差异表达 lncRNA（DElncRNA）与这些 7 个 DEmiRNA 结合。最后，我们发现 7 个 DElncRNA 与总生存率相关（均<0.05）。此外，在 458 个样本中，我们发现 TPX2 表达升高与生存率降低密切相关。单因素和多因素 Cox 分析表明，TPX2 可能是 LUAD 预后的独立因素（<0.05）。然后，通路富集结果表明，TPX2 可能通过参与 LUAD 中的几个与癌症相关的信号通路促进肿瘤发生，尤其是 Notch 信号通路。TPX2 相关的 lncRNA 和 miRNA 与 LUAD 的生存率相关。7 个 lncRNA、7 个 miRNA 和 TPX2 可能作为 LUAD 的预后生物标志物。
