Objective:To investigate the variation,expression and clinical significance of E2F3 gene in melanoma.Methods:Firstly,cBioportal database,Oncomine database and GEO database were used to analyze the variation and expres...Objective:To investigate the variation,expression and clinical significance of E2F3 gene in melanoma.Methods: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 lymphocytes 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 TRMT61B were the top 10 hub genes.YC-1,simvastatin,cytochalasin-d,Deforolimus and cytochalasin-b may be five small molecule compounds for the treatment of melanoma.Conclusion:The mutation and increased expression level of E2F3 gene are related to the poor prognosis of melanoma and participate in the occurrence and development of melanoma by affecting the expression of different tumor immune infiltrating cell subtypes,which may be a potential diagnostic marker and therapeutic target for melanoma.展开更多
基金National Natural Science Foundation of China (No.82060503)。
文摘Objective:To investigate the variation,expression and clinical significance of E2F3 gene in melanoma.Methods: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 lymphocytes 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 TRMT61B were the top 10 hub genes.YC-1,simvastatin,cytochalasin-d,Deforolimus and cytochalasin-b may be five small molecule compounds for the treatment of melanoma.Conclusion:The mutation and increased expression level of E2F3 gene are related to the poor prognosis of melanoma and participate in the occurrence and development of melanoma by affecting the expression of different tumor immune infiltrating cell subtypes,which may be a potential diagnostic marker and therapeutic target for melanoma.
