基于多数据库分析肝细胞癌组织FAM49B基因水平及其临床意义

Clinical significance of cancerous FAM49B gene in patients with hepatocellular carcinoma:an analysis based on multidatabase

目的利用多数据库分析肝细胞癌(HCC)组织FAM49B基因水平及其临床意义。方法利用Oncomine和GEPIA数据库分析HCC组织与正常肝组织FAM49B基因水平,从TCGA获取临床病例资料,应用SPSS 21.0软件统计分析不同临床和病理学特征的HCC组织FAM49B基因水平的异同。自Kaplan Meier Plotter数据库分析不同FAM49B基因水平的HCC患者预后的异同,自MethHC数据库分析FAM49B启动子区甲基化水平,利用String数据库分析与FAM49B相互作用的蛋白网络,采用基因集富集分析(GSEA)预测FAM49B在HCC发病过程中可能的信号调控通路。结果对Oncomine和GEPIA数据库分析显示HCC组织FAM49B基因水平显著高于正常肝组织(P均<0.01);不同性别(P=0.001)、有无肝硬化(P=0.003)、不同肿瘤分化程度(P=0.004)的HCC组织FAM49B基因水平显著不同,而不同年龄、肿瘤大小、病理学分期、甲胎蛋白水平和有无脉管侵犯者无显著性差异(P均>0.05);与FAM49B低水平患者比,FAM49B高水平患者总体生存期显著缩短,具有统计学意义(HR=1.8,P=0.0012);与正常肝组织相比,HCC组织FAM49B启动子区甲基化水平显著降低(P<0.005);与FAM49B相互作用的蛋白有SERPINA1、ISLR和FERMT3;在FAM49B mRNA高水平组织富集到细胞凋亡、细胞周期、调节自噬和P53信号通路等相关基因集(P均<0.05)。结论FAM49B在HCC组织呈高水平,其基因水平与HCC恶性程度和患者不良预后相关,可能作为癌基因在HCC发生发展过程中发挥作用,有望成为HCC诊断及预后评估的新靶点。

Objective The aim of this study was to investigate the clinical significance of cancerous family with sequence similarity 49 member B(FAM49B)gene in patients with hepatocellular carcinoma(HCC).Methods The Oncomine and GEPIA databases were applied to analyze the gene level of FAM49B in HCC tissues and normal liver tissues.HCC dataset was collected from the Cancer Genome Atlas(TCGA)database.The gene levels of FAM49B in patients with different clinic-pathological features were analyed by SPSS 21.0.The impact of FAM49B gene on prognosis was analyzed by Kaplan Meier Plotter.The MethHC database was used to analyze the FAM49B promoter methylation.The String database was used to analyze the network of protein interaction between FAM49B and others,and gene set enrichment analysis(GSEA)was used to predict the possible signal pathways of FAM49B in HCC.Results Studies on Oncomine and GEPIA database showed that FAM49B gene level in HCC tissues was higher than that in normal liver tissues(both P<0.01);the gene levels of FAM49B were different significantly between different gender(P=0.001),with or without cirrhosis(P=0.003)and degree of tumor differentiation(P=0.004),but not between ages,tumor sizes,pathological stages,serum alpha-fetoprotein levels and with or without vascular invasion(all P>0.05);the patients with high cancerous FAM49B level had shorter overall survival than those with low gene level(HR=1.8,P=0.0012);the FAM49B promoter methylation in cancerous tissues was lower than that in normal liver tissues(P<0.005);the proteins interaction with FAM49B included SERPINA1,ISLR and FERMT3,etc.;the samples with high level of FAM49B mRNA showed enrichment of genes in the pathways of apoptosis,cell cycle,regulation of autophagy and P53 signaling pathway(all P<0.05).Conclusion FAM49B is highly expressed in cancerous tissues in patients with HCC,showing a oncogene feature,and those with higher FAM49B gene level is associated with the poor prognosis.