BAP1表达与肿瘤免疫浸润及卵巢癌患者临床预后的关系

Correlation of BAP1 expression with tumor immune infiltration and clinical prognosis of patients with ovarian cancer

目的旨在分析BAP1表达与肿瘤免疫浸润及卵巢癌患者临床预后的关系。方法通过基因组织表达数据库(GTEx)和癌症基因组图谱(TCGA)数据库分析人类泛癌(包括卵巢癌)中BAP1的表达情况。通过单变量生存分析和Kaplan-Meierplotter曲线分析卵巢癌组织中BAP1表达与患者总生存期(OS)、无病生存期(DFS)、无进展生存期(PFS)等预后的关系。基于TISIDB和TIMER数据库和Spearman相关系数分析BAP1与卵巢癌肿瘤浸润淋巴细胞(TILs)及免疫检查点标志分子之间的相关性。最后,从TCGA数据库下载了RNA-Seq数据,选择BAP1及其共同表达基因进行基因集富集分析(GSEA)。结果 BAP1在卵巢癌组织中呈显著高表达(P<0.001),经单变量生存分析和Kaplan-Meier曲线分析,BAP1高表达与患者总生存预后、无病生存预后、无进展生存预后不良有显著相关性(P<0.001)。基于TISIDB数据库和TIMER数据库分析,卵巢癌BAP1与9种TILs丰度和27种常见种免疫检查点标志物表达呈显著正相关性(P<0.05)。基于LinkedOmics平台分析,BAP1高表达与免疫反应激活、适应性免疫应答、B细胞介导的免疫反应、细胞因子生成涉及的炎症反应、免疫反应调节、CD8^(+)T细胞受体(TCR)通路、细胞因子的产生、巨噬细胞激活、NK细胞激活、T细胞介导的免疫反应呈显著正相关(P<0.001)。结论与正常卵巢组织相比,卵巢癌组织中BAP1表达增加。其高表达与患者预后不良及肿瘤免疫浸润有关。这些结果表明BAP1可能在免疫功能调节方面发挥着重要作用,是卵巢癌患者预后的一个潜在生物标志物。

Objective To analyze the relationship between the expression of BAP1 and tumor immune infiltration and the clinical prognosis of ovarian cancer. Methods The expression of BAP1 in human Pan-cancer(including ovarian cancer)was analyzed by Genotype-Tissue Expression(GTEx) and The Cancer Genome Atlas(TCGA) databases. Univariate survival analysis and Kaplan-Meier plotter curves were used to analyze the relationship between the expression of BAP1 and the prognosis of ovarian cancer, including overall survival(OS), disease-free survival(DFS) and progression-free survival(PFS).Relationship between BAP1 and tumor-infiltrating lymphocytes(TILs), immune checkpoint markers was analyzed by TIIDB and TIMER databases and Spearman correlation coefficient. Finally, the RNA-Seq data were downloaded from TCGA database, and BAP1 and its co-expressed genes were selected for gene enrichment analysis(GSEA). Results The expression of BAP1 was significantly high in ovarian cancer(P<0.001). Univariate survival analysis and Kaplan-Meier curve analysis results showed that the expression of BAP1 was significantly associated with the OS, DFS and PFS(P<0.001). BAP1 was significant positively correlated with 9 kinds of TILs abundance and 27 kinds of immune checkpoint markers(P<0.05) on the basis of TISIDB and TIMER databases. Based on LinkedOmics platform analysis, high expression of BAP1 was significant positively correlated with immune response activation, adaptive immune response, B cell mediated immune response, inflammatory response involved in cytokine production, immune response regulation, CD8^(+)T cell receptor(TCR) pathway, cytokine production, macrophage activation, NK cell activation and T cell mediated immune response(P<0.001). Conclusion BAP1 expression increases in ovarian cancer compared with normal tissues. Overexpression of BAP1 is correlated with poor prognosis and immune infiltration. These findings suggest that BAP1 may play an important role in tumor immunity and be a potential prognosis biomarker in patients with ovarian cancer.