Potential Prognostic Biomarkers of Lung Adenocarcinoma Based on Bioinformatic Analysis.

Potential Prognostic Biomarkers of Lung Adenocarcinoma Based on Bioinformatic Analysis.
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基于生物信息学分析的肺腺癌潜在预后生物标志物

DOI:
10.1155/2021/8859996
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发表时间:
2021
影响因子:
--
通讯作者:
Yao C
Yao C
中科院分区:
生物学3区
文献类型:
--
作者:
Hou J;Yao C

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肺腺癌(LUAD)占非小细胞肺癌的60%,诊断不佳,平均5年生存率较低(约20%)。它仍然是全球癌症相关死亡的主要原因。LUAD相关的竞争性内源RNA(ceRNA)网络中的长链非编码RNA(lncRNA)的研究有限。我们的目的是使用生物信息学工具和数据分析来识别LUAD的新的预后生物标志物。我们使用加权相关网络分析系统整合差异表达基因和临床显著模块。我们对收集的候选基因进行了功能分析,并探讨了与LUAD患者总生存率相关的三个LUAD相关基因(VWF,PECAM 1和COL 1A 1)。基于候选mRNA和lncRNA以及差异表达的microRNA的考克斯比例风险分析,我们构建了ceRNA网络,在ceRNA网络中获得了12个lncRNA,并发现了7个新的lncRNA AC021016.2,AC079630.1,AC116407.1,AC125807.2,AF131215.5,LINC 01936和RHOXF 1-AS 1。这些lncRNA被发现与总生存率相关,并适用于Kaplan-Meier生存和受试者工作特征曲线分析的预后预测。特别是,三种lncRNA-AF 131215.5、AC 125807. 2和LINC 01936-显示出LUAD患者总生存期的独立预后价值。我们使用主成分分析和基因集变异分析指数评估了7种lncRNA对LUAD患者的诊断能力。lncRNA和关键基因可以有效地用于区分LUAD肿瘤和正常组织中的基因表达综合谱。特别是,AC021016.2在验证数据集中显示出显著的预后价值。我们的研究结果揭示了使用生物信息学策略探索癌症相关ceRNA中lncRNA的意义。
Lung adenocarcinoma (LUAD), which accounts for 60% of non-small-cell lung cancers, is poorly diagnosed and has a low average 5-year survival rate (approximately 20%). It remains the leading cause of cancer-related deaths worldwide. Studies on long noncoding RNAs (lncRNAs) in LUAD-related competing endogenous RNA (ceRNA) networks are limited. We aimed to identify novel prognostic biomarkers for LUAD using bioinformatic tools and data analysis. We systemically integrated differentially expressed genes and clinically significant modules using weighted correlation network analysis. We performed a functional analysis of the collected candidate genes and explored three LUAD-related genes (VWF, PECAM1, and COL1A1) associated with the overall survival rates of patients with LUAD. Based on Cox proportional hazards analysis of candidate mRNAs and lncRNAs together with differentially expressed microRNAs, we constructed ceRNA networks, obtained 12 lncRNAs in the ceRNA networks, and revealed seven novel lncRNAs AC021016.2, AC079630.1, AC116407.1, AC125807.2, AF131215.5, LINC01936, and RHOXF1-AS1. These lncRNAs were found to be associated with overall survival rates and are suitable for the prediction of prognosis by Kaplan-Meier survival and receiver operating characteristic curve analyses. In particular, three lncRNAs—AF131215.5, AC125807.2, and LINC01936—showed an independent prognostic value of overall survival for patients with LUAD. We evaluated the diagnostic capabilities of seven lncRNAs for patients with LUAD using principal component analysis and the Gene Set Variation Analysis index. lncRNAs and crucial genes could be effectively used for distinguishing LUAD tumors from normal tissues in the Gene Expression Omnibus profile. In particular, AC021016.2 showed a significant prognostic value in the validation dataset. Our findings reveal the significance of exploring lncRNAs in cancer-related ceRNAs using bioinformatic strategies.
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