自噬基因CTSL表达与胶质母细胞瘤患者预后相关  

Autophagy gene CTSL expression correlates with prognosis of patients with glioblastoma

作　　者：夏少怀 李文才 夏学巍[1] 王文波[1] 陈力 XIA Shaohuai;LI Wencai;XIA Xuewei;WANG Wenbo;CHEN Li(Department of Neurosurgery,Affiliated Hospital of Guilin Medical Unviersity,Guilin 541000,Guangxi,China)

机构地区：[1]桂林医学院附属医院神经外科,广西桂林541000

出　　处：《生物信息学》2021年第2期136-148,共13页Chinese Journal of Bioinformatics

基　　金：国家自然科学基金项目(No.81860449);广西自然科学基金项目(No.2016GXNSFCA380028);广西高校科学技术项目(No.LX2014273)。

摘　　要：本研究旨在探讨自噬基因CTSL对胶质母细胞瘤(GBM)患者的预后影响。利用癌症基因组图谱(TCGA)、人类自噬数据库(HADB)、中国脑胶质瘤基因组图谱(CGGA)数据库、基因表达谱分析(GEPIA)获取数据信息,通过筛选差异表达基因及单因素和多因素COX分析确定GBM的独立预后危险因素,同时通过基因本体论(GO)、基因组百科全书途径(KEGG)、临床病理相关性、基因集富集分析(GSEA)、自噬基因网络分析CTSL的相关作用机制。结果显示:(1)富集分析显示胶质母细胞瘤中差异自噬基因(ARG)与自噬体的形成、细胞凋亡、血管生成、细胞化疗等相关;(2)GBM中CTSL的mRNA水平明显高于正常组织样本;(3)多因素COX回归分析显示自噬基因CTSL的高表达为GBM预后的独立危险因素,STUPP治疗(术后替莫唑胺[Tmz]同步放化疗+Tmz辅助化疗)为独立保护因素;(4)自噬基因CTSL在非GCIMP(CpG岛甲基化)型、间质型、IDH野生型、1p/19q无缺失型胶质母细胞瘤及化疗后表达量更高。综上所述,本研究分析了自噬基因在GBM中的作用,并表明自噬基因CTSL的过表达预示胶质母细胞瘤患者不良预后,显示自噬基因CTSL有作为有效靶标的潜质。This study aimed to investigate the prognostic impact of the autophagy gene cathepsin L(CTSL)on patients with glioblastoma(GBM).The Cancer Genome Atlas(TCGA),Human Autophagy Database(HADB),Chinese Glioma Genome Atlas(CGGA)database,and Gene Expression Profiling(GEPIA)were used to obtain data information.The independent prognostic risk factors of GBM were determined by screening differential genes,single factor,and multi-factor COX analysis.At the same time,the CTSL related action mechanisms were analyzed through gene ontology(GO),genome encyclopedia approach(KEGG),clinicopathological correlation analysis,gene set enrichment analysis(GSEA),and autophagy gene network.Results show that(1)Enrichment analysis suggests that the differential autophagy gene(ARG)in GBM was related to the formation of autophagosomes,apoptosis,angiogenesis,and cell chemotherapy.(2)The mRNA level of CTSL in GBM was significantly higher than that of normal tissue samples.(3)Multifactor COX regression analysis shows that the high expression of the autophagy gene CTSL was an independent risk factor for GBM prognosis,and STUPP treatment(Postoperative temozolomide[Tmz]concurrent radiotherapy combined with Tmz adjuvant chemotherapy)was independent protective factor.(4)The expression of autophagy gene CTSL was higher in non-GCIMP(CpG island methylation),mesenchymal,IDH wild,1 p/19 q non-CODEL GBM,and after chemotherapy.In summary,this study analyzed the role of autophagy genes in GBM and results indicate that overexpression of autophagy gene CTSL is a predictor of poor prognosis in patients with GBM.Autophagy gene CTSL has the potential to be an effective target.

关 键 词：自噬基因 CTSL 胶质母细胞瘤 预后 

分 类 号：S857.141[农业科学—临床兽医学]