摘要
目的探讨miR-4746-5p在肝癌中的表达与临床意义。方法从癌症基因组图谱(TCGA)数据库获取375例肝癌组织与50例癌旁组织RNA-seq数据及对应患者的临床信息,比较其miR-4746-5p表达水平与肝癌患者临床病理特征及预后的相关性;使用单、多因素Cox回归模型评估肝癌患者预后的危险因素;应用ROC曲线评估miR-4746-5p诊断肝癌的敏感性;利用ssGSEA评估miR-4746-5p表达水平与肝细胞癌(HCC)免疫浸润水平的相关性。结果miR-4746-5p在肝癌组织中的表达显著高于正常肝组织及癌旁组织(P<0.01),并且miR-4746-5p表达水平与肝癌患者TMN分期、组织学水平、甲胎蛋白水平、是否伴血管侵犯及年龄密切相关(均P<0.05)。高表达miR-4746-5p的肝癌患者总生存率与疾病特异性生存期明显低于miR-4746-5p低表达患者(均P<0.05)。TNM分期与miR-4746-5p表达水平是相互独立的影响肝癌患者预后的危险因素(P<0.01)。GO生物功能及KEGG富集分析提示,miR-4746-5p可能参与调节细胞分化、小GTP酶结合活性和轴突部组装等过程,其靶基因主要富集于MAPK信号通路、轴突引导信号通路、自噬信号通路;miR-4746-5p的表达水平与多种免疫细胞浸润水平(如巨噬细胞、Th2细胞、CD8 T细胞、NK细胞、中性粒细胞等)相关。此外,miR-4746-5p可能通过调控ASPG/CXCL12/IGF2/c11orf96/SEC31B轴促进HCC的发生发展并导致不良预后。结论miR-4746-5p可作为诊断早期肝癌的标志物并对肝癌患者临床治疗及预后预测具有重要意义。
Objective To study the expression and clinical significance of miR-4746-5p in hepatocellular carcinoma(HCC).Methods The RNA-Seq data of 375 HCC tissues and 50 adjacent tissues and the clinical information of corresponding patients were obtained from the Cancer Genome Atlas(TCGA)database.The relationships of miR-4746-5p expression to clinicopathological features and prognosis were analyzed in HCC patients.Univariate and multivariate Cox regression models were used to evaluate the prognostic risk factors.The sensitivity of miR-4746-5p in the diagnosis of HCC was assessed using the ROC curve.The correlation between miR-4746-5p expression and HCC immune infiltration was analyzed by ssGSEA.Results The expression of miR-4746-5p in HCC was significantly higher than that in normal liver tissue and paracancerous tissue(P<0.01).Furthermore,miR-4746-5p expression was closely correlated with TMN stage,histological level,α-fetoprotein level,vascular invasion and age(all P<0.05).The overall survival rate and disease-specific survival time were reduced in patients with high expression of miR-4746-5p when compared to those with low expression of miR-4746-5p(all P<0.05).TNM stage and miR-4746-5p expression level were independent risk factors affecting the prognosis of patients with HCC(P<0.01).GO biological function and KEGG enrichment analysis suggested that miR-4746-5p might be involved in cell differentiation regulation,small GTPase binding activity and axon assembly,and its target genes were mainly enriched in MAPK,axon guidance and autophagy signaling pathways.The expression level of miR-4746-5p was related to the infiltration of a variety of immune cells,such as macrophages,Th2 cells,CD8 T cells,NK cells and neutrophils.In addition,miR-4746-5p might promote the occurrence and development of HCC and result in poor prognosis by regulating ASPG/CXCL12/IGF2/c11orf96/SEC31B axis.Conclusion miR-4746-5p can be used as a marker for the diagnosis of early HCC and is of great significance for the prognosis and clinical treatment.
作者
程兆瑞
程小平
孙诚谊
喻超
CHENG Zhao-rui;CHENG Xiao-ping;SUN Cheng-yi;YU Chao(Graduate School,Expression and Clinical Significance of miR-4746-5p in Hepatocellular Carcinoma:an Analysis Based on TCGA Database;Department of Hepatobiliary Surgery,the Affiliated Hospital,Guizhou Medical University,Guiyang 550000,China;Department of Pathology,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China)
出处
《南昌大学学报（医学版）》
2022年第2期49-55,共7页
Journal of Nanchang University：Medical Sciences
基金
国家自然科学基金项目(81860505,81860506)
贵州省科技计划项目(黔科合支撑[2021]一般080)。
