Molecular characterization of lung cancer: A two-miRNA prognostic signature based on cancer stem-like cells related genes
Molecular characterization of lung cancer: A two-miRNA prognostic signature based on cancer stem-like cells related genes
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肺癌的分子特征：基于癌症干细胞样细胞相关基因的双 miRNA 预后特征
DOI：
10.1002/jcb.29525
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发表时间：
2019-11-06
影响因子：
4
通讯作者：
Liang, Geyu
中科院分区：
文献类型：
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作者：
Cheng, Yanping;Yang, Sheng;Liang, Geyu
肺癌是世界上最致命的癌症之一。为了提高肺癌的生存率，有必要探索特异性预后标志物。越来越多的证据表明非编码RNA与肺癌的生存密切相关，而肿瘤干细胞（cancer stem cells，CSCs）在肺癌的发生发展中也起着重要作用。本研究的目的是寻找影响肺癌预后的CSLCs基因。通过对肿瘤基因组图谱（TCGA）数据库中的长链非编码RNA（lncRNA）、微小RNA（miRNAs）、信使RNA（mRNAs）的差异表达以及CD 326（+）和CD 326（-）A549细胞芯片的差异表达数据进行分析，筛选出稳定一致表达的基因（2个lncRNA、15个miRNAs和134个mRNAs）。通过单变量和多变量考克斯回归分析lncRNA和miRNA的交叉以获得预后基因。两种miRNAs（miR-30 b-5 p和miR-29 c-3 p）与总生存率显著相关。然后利用这两种miRNAs构建风险评分模型作为肺癌的预后标志。随后，我们分析了两种miRNAs与肺癌患者临床信息的相关性，其中T分期、肿瘤恶性度和危险评分（P < .05）可作为肺癌独立的预后指标。最后，对2个miRNAs和134个mRNAs的靶基因进行Gene Ontology注释，并利用京都基因百科全书和基因组通路进行分析，最后利用GEO数据库进行验证。综上所述，本研究阐明了miRNA在CSC促进肺癌发生中的作用，对于寻找肺癌的分子生物标志物具有重要意义。
Lung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326(+) and CD326(-) A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR-30b-5p and miR-29c-3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.