MiR-195通过CCDC88C/ Wnt信号通路调节CD4 + T细胞活化来抑制肺腺癌：一项基于癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和生物信息学分析的研究
MiR-195 restrains lung adenocarcinoma by regulating CD4+ T cell activation via the CCDC88C/Wnt signaling pathway: a study based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and bioinformatic analysis.
作者信息
Yuan Cheng, Xiang Liyang, Bai Rui, Cao Kuo, Gao Yanping, Jiang Xueping, Zhang Nannan, Gong Yan, Xie Conghua
机构信息
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
出版信息
Ann Transl Med. 2019 Jun;7(12):263. doi: 10.21037/atm.2019.05.54.
BACKGROUND
To systematically identity microRNA signatures, as well as miRNA-gene axes, for lung adenocarcinoma (LUAD) and to explore the potential biomarkers and mechanisms associated with the LUAD immune responses.
METHODS
LUAD-related data were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), and these data were then used to identify the differentially expressed miRNAs that were downregulated in tumor tissues. Summary receiver operating characteristic curve analysis, survival analysis and meta-analysis were applied to evaluate the clinical significance and diagnostic value of the identified miRNAs. The presumed targets of the integrated-signature miRNAs were identified via 3 different target prediction algorithms: TargetScan, miRDB and DIANA-TarBase. Immunologic signature gene sets were enriched by gene set enrichment analysis (GSEA). Tumor-infiltrating lymphocytes were profiled by the Tumor IMmune Estimation Resource (TIMER). After pathway enrichment analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, pathway-gene networks were constructed using Cytoscape software.
RESULTS
After integrated analysis of 4 GEO data sets (GSE48414, GSE51853, GSE63805 and GSE74190) and TCGA databases, miR-195 was identified as a potential clinical diagnostic marker. A total of 287 miR-195 target genes were screened, and 3 functional gene sets (GSE13485, GSE21379 and GSE29164) were enriched. GSE21379 was associated with the upregulation of CD4+ T cells in tumors, and the core genes were validated via the TIMER database. The CCDC88C expression level was significantly correlated with CD4+ T cell activation (partial.cor =0.437, P<0.001). Enrichment analysis revealed that CCDC88C was significantly enriched in the Wnt signaling pathway.
CONCLUSIONS
MiR-195, as a suppressor of lung adenocarcinoma, regulates CD4+ T cell activation via CCDC88C.
背景
系统鉴定肺腺癌（LUAD）的微小RNA特征以及微小RNA-基因轴，探索与LUAD免疫反应相关的潜在生物标志物和机制。
方法
从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）获取LUAD相关数据，然后用于鉴定在肿瘤组织中下调的差异表达微小RNA。应用汇总受试者工作特征曲线分析、生存分析和荟萃分析评估鉴定出的微小RNA的临床意义和诊断价值。通过3种不同的靶标预测算法（TargetScan、miRDB和DIANA-TarBase）鉴定整合特征微小RNA的假定靶标。通过基因集富集分析（GSEA）富集免疫特征基因集。利用肿瘤免疫估计资源（TIMER）分析肿瘤浸润淋巴细胞。使用基因本体论和京都基因与基因组百科全书数据库进行通路富集分析后，使用Cytoscape软件构建通路-基因网络。
结果
对4个GEO数据集（GSE48414、GSE51853、GSE63805和GSE74190）和TCGA数据库进行综合分析后，miR-195被鉴定为潜在的临床诊断标志物。共筛选出287个miR-195靶基因，富集了3个功能基因集（GSE13485、GSE21379和GSE29164）。GSE21379与肿瘤中CD4+T细胞的上调相关，核心基因通过TIMER数据库进行了验证。CCDC88C表达水平与CD4+T细胞活化显著相关（偏相关系数=0.437，P<0.001）。富集分析显示CCDC88C在Wnt信号通路中显著富集。
结论
MiR-195作为肺腺癌的抑制因子，通过CCDC88C调节CD4+T细胞活化。
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