基于数据库探索HLA-DPB1基因在泛癌中的潜在价值  

Potential value of HLA-DPB1 gene in pan-cancer based on database

作　　者：王司颖 闫瑞玲[2] 管保章[3] 张伟[1] Wang Siying;Yan Ruiling;Guan Baozhang;Zhang Wei(Department of Breast Surgery,the First Affiliated Hospital of Jinan University,Guangzhou 510630,Guangdong,China;Department of Obstetrics and Gynecology,the First Affiliated Hospital of Jinan University,Guangzhou 510630,Guangdong,China;Department of Nephrology,the First Affiliated Hospital of Jinan University,Guangzhou 510630,Guangdong,China)

机构地区：[1]暨南大学附属第一医院乳腺外科,广东广州510630 [2]暨南大学附属第一医院妇产科,广东广州510630 [3]暨南大学附属第一医院肾脏内科,广东广州510630

出　　处：《暨南大学学报（自然科学与医学版）》2023年第5期478-493,共16页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：广州市科技计划项目(2023A03J0599,2023A03J0568,202201020068)。

摘　　要：目的:探索HLA-DPB1在泛癌中的表达及其对患者预后、肿瘤免疫细胞浸润的影响及作用机制。方法:从UCSC XENA、TCGA数据库获取基因转录组和临床数据,从UALCAN、HPA数据库获取HLA-DPB1蛋白质在泛癌中的表达情况;使用Cox回归和Kaplan-Meier分析评估HLA-DPB1在泛癌中的预后价值;使用ESTIMATE算法和Timer数据库分析HLA-DPB1表达与免疫细胞浸润的相关性;使用cBioPortal数据库分析泛癌中HLA-DPB1的基因突变及其对预后的影响;使用STRING,GEPIA2及R包对HLA-DPB1相关基因进行GO功能注释及KEGG通路富集分析,进一步通过GSEA软件分析HLA-DPB1的生物学功能;采用Cancer SEA数据库分析HLA-DPB1对单个细胞功能状态的影响。结果:HLA-DPB1在大多数肿瘤组织中表达升高,HLA-DPB1高表达与宫颈鳞癌和腺癌(P=0.03)、肾透明细胞癌(P=1.8×10^(-3))、肺腺癌(P=1.0×10^(-4))、子宫内膜癌(P=0.02)、肉瘤(P=4.5×10^(-3))、皮肤黑色素瘤(P=5.6×10^(-7))的良好预后显著相关。HLA-DPB1基因突变存在于多种恶性肿瘤中,是皮肤恶性肿瘤的不良预后因素。HLA-DPB1表达促进肿瘤微环境中的免疫细胞浸润和免疫检查点相关基因的表达。HLA-DPB1可能通过FcεRI介导Ca^(2+)动员、丝裂原活化蛋白激酶(MAPK)激活及NF-κB激活等信号通路参与肿瘤免疫、炎症反应过程。结论:HLA-DPB1的表达水平与不同肿瘤患者的临床预后及免疫细胞浸润高度相关,HLA-DPB1有望成为新的肿瘤预后标志物和免疫治疗的潜在靶点。Objective:To investigate the expression of HLA-DPB1 in pan-cancer,its effect on prognosis,tumor immune infiltration and underlying mechanisms.Methods:The transcriptome and clinical data of HLA-DPB1 were obtained from UCSC XENA,TCGA databases.The expression of HLA-DPB1 protein in pan-carcinoma was obtained from UALCAN and HPA databases.Cox regression and Kaplan-Meier analysis were used to assess the prognostic value of HLA-DPB1 in pan-cancer.The ESTIMATE algorithm and Timer database were applied to explore the relationship between HLA-DPB1 expression and immune infiltration.The cBioPortal database was used to analyze HLA-DPB1 gene mutations and their impact on prognosis in pan cancer.STRING,GEPIA2 and R packages were used to analyz GO functional annotation and KEGG pathway of HLA-DPB1 related genes.The biological function of HLA-DPB1 was analyzed by GSEA software.The Cancer SEA database was used to explore the effect of HLA-DPB1 on the functional state of individual cells.Results:HLA-DPB1 expression was elevated in most tumor tissues.Elevated HLA-DPB1 expression was significantly associated with favorable prognosis in CESC(P=0.03),KIRC(P=1.8×10^(-3)),LUAD(P=1.0×10^(-4)),UCEC(P=0.02),SARC(P=4.5×10^(-3)),and SKCM(P=5.6×10^(-7)).HLA-DPB1 gene mutations were detected in a variety of malignancies and were adverse prognostic factors for skin malignant tumors.HLA-DPB1 expression could promote immune cells infiltration and the expression of immune checkpoint genes in tumor microenvironment.HLA-DPB1 may participate in the immune and inflammatory response process of tumors through FcεRI mediated Ca^(2+)mobilization,MAPK activation and NF-κB activation pathways.Conclusion:The expression level of HLA-DPB1 is highly correlated with the clinical prognosis and immune infiltration of patients with different tumors.HLA-DPB1 is expected to become a new tumor prognostic marker and a potential target for immunotherapy.

关 键 词：HLA-DPB1 泛癌分析 免疫浸润 生存预后 

分 类 号：R73[医药卫生—肿瘤]