γ-干扰素诱导的溶酶体硫醇还原酶在胶质瘤中的表达及其与胶质瘤化疗耐药关系

γ-interferon-inducible lysosomal thiol reductase expression and its relationship with chemotherapy resistance in glioma

目的:探讨γ-干扰素诱导的溶酶体硫醇还原酶(GILT)在胶质瘤中的表达及其与化疗耐药之间的关系。方法:分析美国癌症基因组图谱数据库(TCGA)和中国脑胶质瘤基因谱数据库(CGGA)数据,探讨GILT在胶质瘤组织中的表达,其差异表达与胶质瘤WHO分级、IDH突变、1 p/19 q联合缺失以及生存期的关系。免疫组化检测胶质瘤标本中GILT蛋白的表达情况。分析GILT与经典的化疗耐药基因O 6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)、切除修复交叉互补基因1(ERCC 1)、表皮生长因子2(ERBB 2)的相关性,探讨其与胶质瘤化疗耐药之间的关系。结果:TCGA、CGGA数据库(mRNAseq_325)结果均提示GILT在胶质瘤组织中高表达,且随着胶质瘤WHO分级的增高表达逐级增高。GILT在IDH野生型、非1 p/19 q联合缺失型中表达分别高于IDH突变型及1 p/19 q联合缺失型。不论原发还是复发胶质瘤,GILT高表达患者均具有较短的生存期,且GILT表达与MGMT、ERCC1、ERBB2表达均成正相关,差异均具有统计学意义(P<0.05)。临床胶质瘤标本同样证实GILT在胶质瘤中高表达。结论:GILT在胶质瘤组织中高表达并可能与胶质瘤化疗耐药相关。

Objective:To investigate the expression of gamma-interferon-inducible lysosomal thiol reductase(GILT)and its relationship with chemotherapy resistance in glioma.Methods:By using the data of The Cancer Genome Atlas(TCGA)and Chinese Glioma Genome Atlas(CGGA),the expression level of GILT in glioma and non-tumor brain tissues was analyzed regarding the relationship between differential expression with WHO grade,IDH mutation,1p/19q joint deletion and survival of patients.Immunohistochemistry technique was used to detect the expression of GILT protein in clinical glioma specimens.The correlation between GILT and classic chemotherapy resistance genes in gliomas such as O 6-methylguanine-DNA-methyltransferase(MGMT),excision repaiRcross-complementary gene 1(ERCC 1),epidermal growth factor 2(ERBB 2)were also analyzed.Results:The data analysis of TCGA and CGGA database(mRNAseq_325)showed that GILT was highly expressed in glioma tissues,and the expression was gradually up-regulated with the increase of WHO grade.The expression of GILT in IDH wild type and non-1p/19q combined deletion type was higher than that of IDH mutant type and 1p/19q combined deletion type respectively.Regardless of the primary or recurrent glioma,patients with high expression of GILT had a shorter survival and GILT expression was positively correlated with MGMT,ERCC 1,ERBB 2 expression,and all the differences were statistically significant(P<0.05).Highly expressed GILT in glioma was also confirmed through determination of the clinical glioma specimens.Conclusion:GILT is highly expressed in glioma tissues,and may be related to chemotherapy resistance in gliomas.