基于microRNA-mRNA相互作用的直肠癌预后标志物的研究

Study on prognostic markers of rectal cancer based on microRNA-mRNA interactions

目的:通过microRNA-mRNA相结合探讨直肠癌潜在的关键差异基因和预后标志物。方法:从基因表达汇编公共数据库(GEO)获取microRNA芯片数据,分析获得差异表达microRNAs(DE-miRNAs)及其靶基因。对差异基因进行GO(gene ontology)功能注释和KEGG(kyoto encyclopedia of genes and genomes)通路富集分析,建立差异基因的蛋白质-蛋白质相互作用(PPI)网络,鉴定出关键差异基因,再进一步评估关键差异基因的表达水平和预后作用。结果:总共预测了25个上调和14个下调的DE-miRNAs,对DE-miRNAs的靶基因综合分析后获得了共64个差异基因。共鉴定出10个关键差异基因,GEPIA数据库显示有6个关键差异基因在直肠癌中的表达水平显著高于正常直肠黏膜。经PrognoScan数据库验证,细胞周期蛋白cyclin D1(CCND1)的高表达与结直肠癌较差的预后相关,表达水平和预后的联合分析证明了CCND1的致癌作用。结论:CCND1可能与直肠癌的预后有重要联系,可作为直肠癌预后、药物治疗潜在的新靶点,为后续研究提供新的思路和方向。

Objective: To explore the potential key differential genes and prognostic markers of rectal cancer by microRNA-mRNA.Methods: The microRNA data were obtained from the gene expression database(GEO),and the differentially expressed microRNAs(DE-miRNAs)and their target genes were analyzed.The differential genes were analyzed by GO(gene ontology)functional annotation and KEGG(kyoto encyclopedia of genes and genomes)pathway enrichment analysis,the protein-protein interaction(PPI)network of differential genes was established,the key differential genes were identified,and the expression and prognostic role of key differential genes were further evaluated.Results: 25 up-regulated and 14 down-regulated DE-miRNAs were predicted,and 64 differential genes were obtained after comprehensive analysis of target genes of DE-miRNAs.10 key differential genes were identified.GEPIA database showed that the expression level of 6 key differential genes in rectal cancer were significantly higher than those in normal rectal mucosa.PrognoScan database verified that the high expression of cyclin D1(CCND1)was associated with poor prognosis of colorectal cancer.The combined analysis of expression level and prognosis confirmed the carcinogenic effect of CCND1.Conclusion:CCND1 may have an important relationship with the prognosis of rectal cancer,it can be considered as a potential new target for prognosis and drug therapy of rectal cancer,and it can provide new ideas and directions for follow-up research.