卵巢癌中PTEN基因表达与免疫及预后的相关性研究  

Research on the correlation of PTEN gene with immunity and prognosis in ovarian cancer

作　　者：邹茜 汤妮 张晗婧 刘欢慧 马晓洁[1] ZOU Qian;TANG Ni;ZHANG Hanjing;LIU Huanhui;MA Xiaojie(Department of Oncology,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China)

机构地区：[1]川北医学院附属医院肿瘤科,四川南充637000

出　　处：《临床肿瘤学杂志》2024年第9期879-884,共6页Chinese Clinical Oncology

摘　　要：目的探讨10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN)基因在卵巢癌中的免疫反应及对患者预后的影响。方法通过分析癌症基因组图谱(TCGA)数据库中448例卵巢癌组织和非肿瘤组织的PTEN mRNA数据,探讨基因突变、甲基化与表达水平之间的关系,并评估PTEN表达对卵巢癌患者预后的影响。采用TISIDB、TIME2.0、cBioPortal、GSEA等数据库,分析PTEN水平与免疫相关基因、相关通路的关系,以及其与免疫细胞亚群和肿瘤浸润免疫之间的关系。结果与非肿瘤组织比较,PTEN的表达在卵巢癌组织中显著降低(P<0.01),且与其甲基化水平呈负相关(r=-0.12,P<0.001)。PTEN高表达的卵巢癌患者的总生存时间明显短于低表达患者(P=1.2×10^(-4))。PTEN表达与大多数免疫抑制因子、免疫刺激因子、MHC相关基因、趋化因子及趋化因子受体基因的表达呈正相关。此外,PTEN表达与免疫检查点分子B7-H3呈正相关,且与肿瘤微环境中的CD8^(+)T细胞、巨噬细胞、CD4^(+)记忆细胞、巨细胞等免疫细胞亚群存在显著相关性。GSEA分析表明,PTEN高表达组中一些与免疫相关的通路,如血清补体、白细胞介素2、白细胞介素6等被激活。结论PTEN基因高表达与卵巢癌患者预后不良有关,且可能通过调节肿瘤微环境中的免疫细胞亚群以及参与卵巢癌的免疫逃逸来发挥作用。Objective To investigate the role of gene of phosphates and tensin homologue deleted on chromosome ten(PTEN)gene in the immune response and prognosis of ovarian cancer patients.Methods By analyzing the PTEN mRNA data of 448 ovarian cancer tissues and non-tumor tissues from the TCGA database,the relationships between gene mutations,methylation,and expression levels were analyzed,and the impact of PTEN expression on ovarian cancer patients’prognosis was further evaluated.The TISIDB,TIME2.0,cBioPortal,and GSEA databases were used to analyze the relationships between PTEN levels and immune-related genes,pathways,immune cell subpopulations,and tumor infiltrating immunity.Results Compared with non-tumor tissues,PTEN mutations and copy number were significantly increased in ovarian cancer tissues(P<0.01),and were negatively correlated with methylation levels(r=-0.12,P<0.001).Patients with high PTEN expression had significantly shorter overall survival than those with low expression(P=1.2×10^(-4)).PTEN expression was positively correlated with the expression of most immune inhibitory factors,immune stimulatory factors,MHC-related genes,chemokines,and chemokine receptor genes.Furthermore,PTEN expression was positively correlated with the expression of the immune checkpoint molecule B7-H3,and was significantly correlated with immune cell subpopulations such as CD8^(+)T cells,macrophages,CD4^(+)memory cells,and giant cells in the tumor microenvironment.GSEA analysis showed that some immune-related pathways,such as the complement system,interleukin-2,and interleukin-6,were activated in the PTEN high-expression group.Conclusion High PTEN expression is associated with poor prognosis in ovarian cancer patients and may play a role in regulating immune cell subpopulations in the tumor microenvironment and in promoting immune evasion in ovarian cancer.

关 键 词：卵巢癌 10号染色体上缺失的磷酸酶和张力蛋白同源物 免疫 预后 

分 类 号：R737.31[医药卫生—肿瘤]