Four-miRNA signature as a prognostic tool for lung adenocarcinoma.
Four-miRNA signature as a prognostic tool for lung adenocarcinoma.
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DOI：
10.2147/ott.s155016
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发表时间：
2018
影响因子：
4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Lin Y;Lv Y;Liang R;Yuan C;Zhang J;He D;Zheng X;Zhang J
本研究的目的是产生一种新的miRNA表达特征来准确预测肺腺癌(LUAD)患者的预后。使用从癌症基因组图谱数据库下载的表达谱，我们鉴定了在LUAD和配对的健康组织中差异表达的多个miRNAs。然后，我们使用单变量/多变量Cox回归分析来评估差异表达的miRNA的预后价值。这一分析最终被用来构建一个有效预测患者生存的四个miRNA签名。最后，我们利用基因本体论和京都百科全书的基因和基因组途径富集法分析了这四个miRNAs的靶基因的潜在功能。根据我们的截断标准(P<；0.05和|log2FC|>；1.0)，我们总共确定了187个差异表达的miRNAs，其中148个在LUAD组织中上调，39个在LUAD组织中下调。Kaplan-Meier分析显示，有4个miRNAs(miR-148A-5p、miR-31-5p、miR-548v和miR-550A-5p)与生存相关。我们根据这四个miRNAs的表达生成了一个签名指数，并将患者分成低风险组和高风险组。高危组患者的生存时间明显短于低危组(P=0.002)。功能浓缩分析表明，这四个miRNAs的靶基因参与了蛋白质磷酸化以及河马和鞘脂信号转导途径。综上所述，我们的结果表明，我们的4-miRNA签名可以作为LUAD患者的预后工具。
The aim of this study was to generate a novel miRNA expression signature to accurately predict prognosis for patients with lung adenocarcinoma (LUAD). Using expression profiles downloaded from The Cancer Genome Atlas database, we identified multiple miRNAs with differential expression between LUAD and paired healthy tissues. We then evaluated the prognostic values of the differentially expressed miRNAs using univariate/multivariate Cox regression analysis. This analysis was ultimately used to construct a four-miRNA signature that effectively predicted patient survival. Finally, we analyzed potential functional roles of the target genes for these four miRNAs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Based on our cutoff criteria (P<0.05 and |log2FC| >1.0), we identified a total of 187 differentially expressed miRNAs, including 148 that were upregulated in LUAD tissues and 39 that were downregulated. Four miRNAs (miR-148a-5p, miR-31-5p, miR-548v, and miR-550a-5p) were independently associated with survival based on Kaplan–Meier analysis. We generated a signature index based on the expression of these four miRNAs and stratified patients into low- and high-risk groups. Patients in the high-risk group had significantly shorter survival times than those in the low-risk group (P=0.002). A functional enrichment analysis suggested that the target genes of these four miRNAs were involved in protein phosphorylation and the Hippo and sphingolipid signaling pathways. Taken together, our results suggest that our four-miRNA signature can be used as a prognostic tool for patients with LUAD.