中国肿瘤生物治疗杂志2023，Vol.30Issue(11)：997-1008,12.DOI:10.3872/j.issn.1007-385x.2023.11.010
谷胱甘肽过氧化物酶家族的功能及其成员作为胶质瘤免疫治疗标志物的可能性
The function of the glutathione peroxidase family and the possibility of its members as immunotherapeutic markers for glioma
摘要
Abstract
Objective:To explore the biological function and prognostic value of the glutathione peroxidase(GPX)family in gliomas.Methods:The correlation of gene expression of GPX isoforms in gliomas,protein interactions,gene mutations,the relationship between GPX expression and the prognosis of glioma patients,and the gene set enrichment analysis of GPX7 and 8 were analyzed using various databases such as TCGA,GTEx,and CGGA;the correlation analysis of the expression of GPX8 with the immune cell infiltration and the expression of immune checkpoint molecules in glioma;and the correlation analysis of GPX8 expression with IC50 of chemotherapeutic agents in glioma.The correlation between GPX8 expression and IC50 of chemotherapeutic drugs was analyzed;the expression of GPX mRNA,protein and related immune checkpoint molecules in glioma tissues and control tissues of Chinese people(Specimens were collected from five cases of glioma and three cases of severe traumatic brain injury surgically removed by neurosurgery at Fengxian District Central Hospital,Shanghai,China,between October 20,2022 and December 20,2022.)were detected by qPCR,WB and immunofluorescence techniques for validation.Results:Database analysis showed that there were interactions and correlation of gene expression levels among GPX isoforms in gliomas(P<0.05 or P<0.01),and there were single-nucleotide and copy-number variations of several GPX isoforms in glioma tissues;there were significant differences of GPX isoforms in different types of immune cells and tumor cells of glioma tissues;and high expression levels of GPX1,4,7,and 8(all P<0.05)were correlated with poor prognosis of glioma patients(P<0.01).7 and 8 were highly expressed in glioma tissues(all P<0.05),and correlated with poor prognosis of glioma patients(P<0.01);qPCR and WB assays for GPX7 and 8 expression in human glioma tissues verified the correctness of the database information;the expression of GPX7 and 8 in gliomas has an independent prognostic value;GSEA analysis showed that GPX7 and 8 are associated with the glioma cell cycle and the immune pathway;GBM and LGG are associated with GBM and LGG;and GPX7 and 8 are associated with GBM and LGG are associated with GBM and LGG.related;GPX8 expression was significantly correlated with immune scores in GBM and LGG(P<0.01);GPX8 may induce infiltration of suppressive immune cells in gliomas leading to immunosuppression;there was a positive correlation between GPX8 expression and the expression of several immune checkpoint molecules in gliomas(P<0.01);there was a significant positive correlation between GPX8 expression and the IC50 of the chemotherapeutic agents(P<0.01),and its high expression could lead to the resistance of glioma to chemotherapeutic drugs.Conclusion:GPX8 expression is significantly high in gliomas,and GPX8 expression may induce infiltration of suppressor immune cells in gliomas,which is strongly associated with multiple immunosuppression points,with the IC50 of multiple chemotherapeutic agents,and with patient prognosis,which may serve as a potential target for immunotherapy of gliomas.关键词
胶质瘤/谷胱甘肽过氧化物酶/免疫浸润/谷胱甘肽过氧化物酶8/免疫检查点/耐药Key words
glioma/glutathione peroxidase(GPX)/immune infiltration/GPX8/immune checkpoint/drug resistance分类
医药卫生引用本文复制引用
李光明,张园园,乔晓龙,宋大勇..谷胱甘肽过氧化物酶家族的功能及其成员作为胶质瘤免疫治疗标志物的可能性[J].中国肿瘤生物治疗杂志,2023,30(11):997-1008,12.基金项目
上海市科委科研基金(No.19411968200) （No.19411968200）
