摘要
目的基于中国脑胶质瘤基因组图谱计划(CGGA)和癌症基因组图谱计划(TCGA)数据库分析非受体型蛋白酪氨酸磷酸酶12基因(PTPN12)在脑胶质瘤中的表达和意义。方法回顾性分析CGGA数据库(325例)和TCGA数据库(636例)中脑胶质瘤患者的临床资料和RNA测序数据。分析不同世界卫生组织(WHO)肿瘤级别、四分型亚型、异柠檬酸脱氢酶(IDH)突变状态、O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化状态的患者PTPN12表达量的差异。根据PTPN12的表达量将患者分为PTPN12高表达组和PTPN12低表达组,采用Kaplan-Meier法绘制生存曲线,比较两组患者的生存差异。采用单因素和多因素Cox回归分析法判断PTPN12对脑胶质瘤患者的预后作用。进一步通过基因本体(GO)功能富集分析及京都基因和基因组百科全书(KEGG)通路富集分析获得基因相关的功能以及有关的通路。结果两数据库中,PTPN12的表达量均随脑胶质瘤病理级别的升高而升高(均P<0.01);与IDH突变型比较,IDH野生型中PTPN12表达量升高(均P<0.01);MGMT启动子非甲基化者PTPN12表达量高于MGMT启动子甲基化者(均P<0.01);PTPN12在经典型、间质型、神经元型以及前神经元型中表达量的差异均具有统计学意义,间质型中表达量最高(均P<0.01)。两数据库中,PTPN12高表达者均比低表达者的生存期短(均P<0.01)。两个数据库中,多因素Cox回归分析结果均显示,PTPN12表达量为脑胶质瘤患者生存期的独立影响因素(CGGA数据库中,HR=1.433,95%CI:1.094~1.876,P=0.009;TCGA数据库中,HR=1.588,95%CI:1.018~2.477,P=0.042)。GO分析结果显示,PTPN12表达量正相关的基因更多地富集在增殖、凋亡、黏附、蛋白水解、免疫反应、血管生成、药物反应、缺氧反应、肿瘤细胞G2/M期的转化、肿瘤细胞G1/S期的转化等多个与脑胶质瘤恶性进展相关的功能上。KEGG分析结果显示,与PTPN12表达量呈正相关的基因更多地富集在肿瘤�
Objective To analyze the expression and significance of protein tyrosine phosphatase non-receptor type 12(PTPN12)in gliomas based on the Chinese Glioma Genome Atlas(CGGA)and the Cancer Genome Atlas(TCGA)datasets.Methods We retrospectively analyzed the clinical data and RNA sequencing data of glioma patients in the CGGA dataset(325 cases)and TCGA dataset(636 cases).We measured the different expression levels of PTPN12 in glioma patients with different World Health Organization(WHO)grades,subtypes,isocitrate dehydrogenase(IDH)mutation status and O6-meth-ylguanine-DNA methyltransferase(MGMT)promoter methylation status.According to the expression level of PTPN12,the patients were divided into PTPN12 high-expression group and PTPN12 low-expression group.Kaplan-Meier survival curve was used to compare the survival between the two groups.Univariate and multivariate Cox regression analysis were used to determine the prognostic effect of PTPN12 in glioma patients.Gene ontology(GO)function enrichment analysis and the Kyoto Encyclopedia of Genes and Genome(KEGG)pathway enrichment analysis were further used to analyze the related functions and pathways.Results In the two datasets,the expression level of PTPN12 increased with the increase of the glioma grade(all P<0.01).The expression level of PTPN12 in the IDH wild type was elevated compared with the IDH mutant type(all P<0.01).The expression level of PTPN12 in MGMT promoter unmethylated type was higher than that in MGMT promoter methylated type(all P<0.01).The expression level of PTPN12 was highest in mesenchymal subtype than the other subtypes(all P<0.01).In the two datasets,the patients with high PTPN12 expression had a shorter survival time than those with low PTPN12 expression(both P<0.01).The results of multivariate Cox regression analysis showed that the expression level of PTPN12 was an independent prognostic factor of patients with gliomas(CGGA dataset,HR=1.433,95%CI:1.094-1.876,P=0.009;TCGA dataset,HR=1.588,95%CI:1.018-2.477,P=0.042).GO analysis results showed that
作者
黄华
王宽宇
Huang Hua;Wang Kuanyu(Beijing Neurosurgical Institute,Capital Medical University,Beijing 100070,China)
出处
《中华神经外科杂志》
CSCD
北大核心
2021年第1期75-80,共6页
Chinese Journal of Neurosurgery
基金
国家自然科学基金(82003192)。
