Characterization of lncRNA-Associated ceRNA Network to Reveal Potential Prognostic Biomarkers in Lung Adenocarcinoma
Characterization of lncRNA-Associated ceRNA Network to Reveal Potential Prognostic Biomarkers in Lung Adenocarcinoma
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DOI：
10.3389/fbioe.2020.00266
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发表时间：
2020-04-17
影响因子：
5.7
通讯作者：
Ma, Lixin
中科院分区：
文献类型：
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作者：
Wang, Yang;He, Ruyi;Ma, Lixin
肺腺癌（LUAD）是危害人类健康最致命的恶性肿瘤之一。LUAD患者长链非编码RNA （lncRNA）相关的竞争内源性RNA （ceRNA）网络的复杂性和行为特征尚不清楚。本研究的目的是阐明异常rna的调控网络，观察和识别LUAD中涉及的潜在预后特征。mrna、lncrna和mirna的表达谱从TCGA数据库中获得。共筛选出2078个demrna、257个delncrna和101个demirna。构建了包含45个demmrna的PPI网络。在PPI网络中发现了10个与细胞周期相关通路相关的枢纽基因，它们在调节细胞增殖中发挥了关键作用。共有3个demirna、7个delncrna和6个demmrna被纳入到ceRNA网络中。除了某些未发表研究报告的基因外，ceRNA网络中的所有基因在LUAD中都在控制肿瘤细胞增殖中发挥重要作用，并与预后相关。最后，基于逐步回归和Cox回归生存分析，我们确定了miR490、miR1293、LINC01740和IGF2BP1 4个候选生物标志物，并建立了基于这4个基因的风险模型。我们的研究为lncrna相关的ceRNA网络提供了一个全局的视角和系统的解剖，鉴定的四个基因可能是参与LUAD发病机制的新的重要预后因素。
Lung adenocarcinoma (LUAD) is one of the most fatal malignant tumors harmful to human health. The complexity and behavior characteristics of long-non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in LUAD patients are still unclear. The purpose of this study was to elucidate the regulatory networks of dysregulated RNAs, view, and identify potential prognosis signatures involved in LUAD. The expression profiles of mRNAs, lncRNAs, and miRNAs were obtained from the TCGA database. In total, 2078 DEmRNAs, 257 DElncRNAs, and 101 DEmiRNAs were sorted out. A PPI network including 45 DEmRNAs was constructed. Ten hub genes in the PPI network associated with cell cycle-related pathways were identified and they played key roles in regulating cell proliferation. A total of three DEmiRNAs, seven DElncRNAs, and six DEmRNAs were enrolled in the ceRNA network. Except for certain genes without any published study reports, all the genes in the ceRNA network played an essential role in controlling tumor cell proliferation and were associated with prognosis in LUAD. Finally, based on step regression and Cox regression survival analysis, we identified four candidate biomarkers, including miR490, miR1293, LINC01740, and IGF2BP1, and established a risk model based on the four genes. Our study provided a global view and systematic dissection of the lncRNA-associated ceRNA network, and the identified four genes might be novel important prognostic factors involved in LUAD pathogenesis.