通过整合基因组学分析鉴定微小RNA作为肺腺癌潜在生物标志物
Identification of microRNAs as potential biomarkers for lung adenocarcinoma using integrating genomics analysis.
作者信息
Peng Zhuo, Pan Longfei, Niu Zequn, Li Wei, Dang Xiaoyan, Wan Lin, Zhang Rui, Yang Shuanying
机构信息
Department of Emergency Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Department of Respiratory Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
出版信息
Oncotarget. 2017 Jul 18;8(38):64143-64156. doi: 10.18632/oncotarget.19358. eCollection 2017 Sep 8.
Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer, but novel biomarkers for early diagnosis are lacking. Extensive effort has been exerted to identify miRNA biomarkers in LUAD. Unfortunately, high inter-lab variability and small sample sizes have produced inconsistent conclusions in this field. To resolve the above-mentioned limitations, we performed a comprehensive analysis based on LUAD miRNome profiling studies using the robust rank aggregation (RRA) method. Moreover, miRNA-gene interaction network, pathway enrichment analysis and Kaplan-Meier survival curves were used to investigate the clinical values and biological functions of the identified miRNAs. A total of six common differentially expressed miRNAs (DEMs) were identified in LUAD. An independent cohort further confirmed that four miRNAs (miR-21-5p, miR-210-3p, miR-182-5p and miR-183-5p) were up-regulated and two miRNAs (miR-126-3p and miR-218-5p) were down-regulated in LUAD tissues. Pathway enrichment analysis also suggested that the above-listed six DEMs may affect LUAD progression via the estrogen signaling pathway. Survival analysis based on the TCGA dataset revealed the potential prognostic values of six DEMs in patients with LUAD (-value<0.01). In conclusion, we identified a panel of six miRNAs from LUAD using miRNome profiling studies. Our results provide evidence for the use of these six DEMs as novel diagnostic and prognostic biomarkers for LUAD patients.
肺腺癌(LUAD)是非小细胞肺癌最常见的组织学亚型,但缺乏用于早期诊断的新型生物标志物。人们已付出巨大努力来识别LUAD中的miRNA生物标志物。不幸的是,实验室间的高度变异性和小样本量在该领域产生了不一致的结论。为解决上述局限性,我们使用稳健秩聚合(RRA)方法,基于LUAD的miRNome分析研究进行了全面分析。此外,还利用miRNA-基因相互作用网络、通路富集分析和Kaplan-Meier生存曲线来研究已识别miRNA的临床价值和生物学功能。在LUAD中总共鉴定出6种常见的差异表达miRNA(DEM)。一个独立队列进一步证实,在LUAD组织中,4种miRNA(miR-21-5p、miR-210-3p、miR-182-5p和miR-183-5p)上调,2种miRNA(miR-126-3p和miR-218-5p)下调。通路富集分析还表明,上述6种DEM可能通过雌激素信号通路影响LUAD的进展。基于TCGA数据集的生存分析揭示了6种DEM对LUAD患者的潜在预后价值(P值<0.01)。总之,我们通过miRNome分析研究从LUAD中鉴定出一组6种miRNA。我们的结果为将这6种DEM用作LUAD患者的新型诊断和预后生物标志物提供了证据。