miR-621在肝细胞癌组织中的表达及其临床意义

Expression of miR-621 in Hepatocellular Carcinoma and Its Clinical Significance

[目的]探讨肝细胞癌(hepatocellular carcinoma,HCC)组织中miR-621的表达及其临床意义,并对miR-621靶基因进行系统的生物信息学分析。[方法]基于GEO(Gene Expression Omnibus)和TCGA(The Cancer Genome Atlas)数据库,比较HCC组织和癌旁组织中miR-621表达量,并分析miR-621表达与HCC患者临床病理特征及预后的相关性。利用生物信息学方法对miR-621的靶基因进行预测及功能富集分析,并结合蛋白互作网络及预后分析结果筛选miR-621关键靶基因。[结果] miR-621在HCC组织中较癌旁组织低表达(P<0.05)。HCC组织中miR-621表达量与患者TNM分期、肿瘤分化程度以及血清甲胎蛋白(AFP)等指标显著相关(P均<0.05)。生存分析显示HCC组织中miR-621低表达是影响患者预后的独立危险因素(P<0.05)。富集分析提示miR-621的靶基因主要富集于细胞黏附、氨基酸跨膜运输、钙离子结合等功能,以及MAPK、细胞周期等信号通路。AURKA、CDC25A、ESPL1、GINS2、KIF20B、MCM5、NUSAP1、OIP5等为miR-621关键靶基因,其在HCC组织中均呈现表达上调,且相对高表达者预后不良(P均<0.05)。[结论] miR-621可作为一种抑癌基因参与HCC的发生、发展,并具有成为HCC诊断标志物、预后指标及治疗靶点的潜在价值。

[Objective] To analyze the expression of miR-621 and its clinical significance in patients with hepatocellular carcinoma(HCC) using the data from GEO and TCGA. [Methods] The expression levels of miR-621 in HCC tissues and its adjacent liver tissues were compared with data from GEO and TCGA database,and the relations of miR-621 expression level with clinicopathologic characteristics and prognosis of the patients were also analyzed. The prediction of potential target genes of miR-621 and the functional enrichment analyses of the target genes were performed by bioinformatics analysis. Furthermore,the key target genes of miR-621 were screened based on PPIs network and survival analysis. [Results] The expression levels of miR-621 were significantly downregulated in HCC tissues compared to the adjacent liver tissues(P<0.05). The expression level of miR-621 was positively correlated with TNM stage,pathological tumor grade and alpha-fetoprotein(all P<0.05). Survival analysis showed that low expression of miR-621 was associated with poor prognosis in patients with HCC(P<0.05). Enrichment analyses revealed that the target genes of miR-621 were significantly associated with cell adhesion,calcium ion binding,amino acid transmembrane transporter activity,MAPK pathway and cell cycle signaling pathway. AURKA,CDC25 A,ESPL1,GINS2,KIF20 B,MCM5,NUSAP1 and OIP5 were the key target genes of miR-621,with significant upregulation in HCC tissues(all P<0.05). Patients with high expression of these genes had relatively poor prognosis(all P<0.05). [Conclusion] Mi R621 may play as an anti-oncogene miRNA in HCC,and it has a potential value of acting as a diagnostic biomarker,prognostic indicator and therapeutic target for HCC.