基于多种数据库分析E2F3基因在黑色素瘤中的变异、表达及临床意义  

Analysis of E2F3 gene variants,expression and clinical significance in melanoma based on multiple databases

作　　者：韩利民 叶钢 邓川 代姣 赵海龙 HAN Li-min;YE Gang;DENG Chuan;DAI Jiao;ZHAO Hai-long(Department of Endocrine,People’s Hospital of Changshou District,Chongqing 401220,China;Department of Hepatobiliary Surgery,People’s Hospital of Changshou District,Chongqing 401220,China;Department of Neurology,People’s Hospital of Changshou District,Chongqing 401220,China;Department of Pharmacy,People’s Hospital of Changshou District,Chongqing 401220,China;Department of Pathophysiology,School of Basic Medical Sciences,Zunyi Medical University,Zunyi 563000,China)

机构地区：[1]重庆市长寿区人民医院内分泌内科,重庆401220 [2]重庆市长寿区人民医院肝胆外科,重庆401220 [3]重庆市长寿区人民医院神经内科,重庆401220 [4]重庆市长寿区人民医院药学部,重庆401220 [5]遵义医科大学基础医学院病理生理学教研室,贵州遵义563000

出　　处：《海南医学院学报》2023年第20期1563-1573,共11页Journal of Hainan Medical University

基　　金：国家自然科学基金(82060503)。

摘　　要：目的:探究E2F3基因在黑色素瘤中的变异、表达及临床意义。方法:首先,采用cBioportal数据库、Oncomine数据库、GEO数据库分析E2F3基因在黑色素瘤中的变异情况和表达水平,OSskcm数据库和TISIDB数据库分析E2F3与黑色素瘤的预后和肿瘤免疫浸润细胞的关系。接着,采用LinkedOmics数据库鉴定黑色素瘤中与E2F3表达相关的差异基因并进行生物学功能分析,利用Cytoscpae筛选Hub基因。最后,通过CMap数据库筛选治疗黑色素瘤的小分子化合物。结果:E2F3基因在黑色素瘤中的变异率为约4%,突变位点有21个。与正常皮肤组织相比,E2F3基因在黑色素瘤中的表达明显升高(P<0.01)。E2F3基因的变异和表达水平升高与黑色素瘤患者的总生存期(OS)缩短有关(P<0.05)。E2F3的CNA水平与pDC、Neutrophil、Act DC、Th17等淋巴细胞的表达水平呈负相关,与CXCL5、CCL13、CCR1等趋化因子的表达水平呈负相关。E2F3的甲基化水平与Th1、Neutrophil、Act DC等淋巴细胞的表达水平呈正相关,与CXCL16、CXCL12、CCR1等趋化因子的表达水平呈正相关。E2F3的表达水平与Th17、Tcm CD4、Th1等淋巴细胞的表达水平呈负相关,与CXCL 16、CCL 22、CCL 2等趋化因子的表达水平呈负相关。黑色素瘤中UHRF1BP1等96个基因的表达与E2F3的表达呈显著相关(|cor|≥0.5,P<0.05),以上基因主要与RNA转运、真核生物的核糖体生物生成、细胞周期等通路有关;其中,WDR12、WDR43、RBM28、UTP18、DKC1、PAK1IP1、DDX31、TEX10、TRUB1、TRMT61B是前10位hub基因。YC-1、辛伐他汀、细胞松弛素-d、Deforolimus和细胞松弛素-b可能是治疗黑色素瘤的5种潜在小分子化合物。结论:E2F3基因突变和表达水平升高与黑色素瘤的不良预后有关,可通过影响不同肿瘤免疫浸润细胞亚型的表达参与黑色素瘤的发生和发展,其可能是黑色素瘤的潜在诊断标志物和治疗靶点。Objective:To investigate the variation,expression and clinical significance of E2F3 gene in melanoma.Meth⁃ods:Firstly,cBioportal database,Oncomine database and GEO database were used to analyze the variation and expression level of E2F3 gene in melanoma.OSskcm database and TISIDB database were used to analyze the relationship between E2F3 and melanoma prognosis and tumor immune infiltrating cells.Then,the LinkedOmics database was used to identify the differential genes related to E2F3 expression in melanoma and analyze their biological functions.Finally,small molecule compounds for the treatment of melanoma were screened through the CMap database.Results:The mutation rate of E2F3 gene in melanoma is about 4%,and there are 21 mutation sites.Compared with normal skin tissues,the expression of E2F3 gene in melanoma was significantly increased(P<0.01).The mutation and increased expression of E2F3 gene were associated with the shortened overall survival(OS)of melanoma patients(P<0.05).The CNA level of E2F3 was negatively correlated with the expression levels of lym-phocytes such as pDC,Neutrophil,Act DC and Th17,and negatively correlated with the expression levels of chemokines such as CXCL5,CCL13 and CCR1.The methylation level of E2F3 was positively correlated with the expression levels of Th1,Neutrophil,Act DC and other lymphocytes,and positively correlated with the expression levels of CXCL16,CXCL12,CCR1 and other chemokines.The expression level of E2F3 was negatively correlated with the expression levels of lymphocytes such as Th17,Tcm CD4 and Th1,and negatively correlated with the expression levels of chemokines such as CXCL 16,CCL 22 and CCL 2.The expression of 96 genes such as UHRF1BP1 in melanoma was significantly correlated with the expression of E2F3(|cor|≥0.5,P<0.05).The above genes were mainly related to RNA transport,eukaryotic ribosome biogenesis,cell cycle and other pathways.Among them,WDR12,WDR43,RBM28,UTP18,DKC1,PAK1IP1,DDX31,TEX10,TRUB1 and TRMT61 B were the top 10 hub genes.YC-1,simvastatin,cyto

关 键 词：黑色素瘤 E2F3 数据库 突变 免疫浸润 预后 

分 类 号：R739.5[医药卫生—肿瘤]