Expression and clinical significant of pyruvate dehydrogenase kinase 1 in gliomas based on the Cancer Genome Atlas by bioinformatics analysis

Q4 Medicine

中华神经外科杂志 Pub Date : 2020-03-28 DOI:10.3760/CMA.J.CN112050-20190203-00035

F. Yuan, Xiaoguang Fan, Zhen Yang, Tao Li, L. Yi, Yihan Yang, Hao-lang Ming, Bingcheng Ren, Sheng-ping Yu

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Abstract

Objective To investigate the molecular and clinical features of PDK1 (pyruvate dehydrogenase kinase 1) in gliomas based on the Cancer Genome Atlas (TCGA) by bioinformatics analysis. Methods The clinical data of 641 glioma patients in TCGA database were retrospectively analyzed. The online analysis website of GEPIA (http: //gepia.cancer-pku.cn/) was used to analyze PDK1 expression in glioma patients. Pearson correlation analysis was performed to create a gene list related to PDK1. The online analysis tool STRING was used to analyze the interaction network of the differential genes. According to the degree of confidence, the top key proteins were screened. The function of PDK1-related differential genes and its relationship with the kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were explored by gene ontology (GO) analysis. According to PDK1 protein expression, all patients were divided into PDK1 protein low expression group (380 cases) and PDK1 protein high expression group (261 cases). Kaplan-Meier survival curves were used to compare the survival differences between the two groups of patients. Univariate and multivariate Cox regression analysis were used to determine the effect of PDK1 protein expression on the prognosis of patients with glioma. Results The expression of PDK1 protein in 641 glioma patients in TCGA database showed that the expression level in the World Health Organization(WHO) Ⅳ glioma (8.86±0.90) was higher than that in grade Ⅱ (7.24±0.60) and grade Ⅲ (7.34±0.80)(P 0.05). The cumulative survival rate of glioma patients in the PDK1 high-expression group was significantly lower than that in the PDK1 low-expression group (P<0.05). Pearson correlation test analysis revealed that 96 genes were closely related to PDK1 expression, of which 69 were positively correlated and 27 were negatively correlated. GO analysis and KEGG pathway analysis showed that PDK1 participated in many important biological processes, which were closely related to the hypoxia microenvironment, reaction to organic cyclic compounds, reaction to organic nitrogen compounds, response to cAMP and the HIF-1 signaling pathway. Multivariate analysis showed that age (HR=1.579, 95% CI: 1.085-2.299, P=0.017), WHO grade (HR=12.106, 95% CI: 6.521-22.474, P<0.001) and radiotherapy (HR=0.502, 95% CI: 0.325-0.775, P=0.002) were independent influencing factors for the survival of glioma patients (all P <0.05) and could be used independently to explore the prognosis of patients.However, PDK1 protein expression does not affect the prognosis of glioma patients. Conclusion PDK1 expression is different in glioma patients with different WHO pathological levels, and mainly related to hypoxia and HIF-1 signaling pathway. Key words: Glioma; Prognosis; The cancer genome atlas; Pyruvate dehydrogenase kinase 1

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基于癌症基因组图谱的丙酮酸脱氢酶激酶1在胶质瘤中的表达及其临床意义

目的利用癌症基因组图谱（TCGA），通过生物信息学分析，探讨胶质瘤中丙酮酸脱氢酶激酶1（PDK1）的分子和临床特征。方法回顾性分析TCGA数据库中641例胶质瘤患者的临床资料。利用GEPIA在线分析网站（http://GEPIA.cancer-pku.cn/）对胶质瘤患者PDK1的表达进行分析。进行Pearson相关分析以创建与PDK1相关的基因列表。在线分析工具STRING用于分析差异基因的相互作用网络。根据置信度，筛选出最关键的蛋白质。通过基因本体论（GO）分析探讨了PDK1相关差异基因的功能及其与京都基因与基因组百科全书（KEGG）通路的关系。根据PDK1蛋白表达，将所有患者分为PDK1蛋白低表达组（380例）和PDK1蛋白高表达组（261例）。Kaplan-Meier生存曲线用于比较两组患者的生存差异。采用单变量和多变量Cox回归分析来确定PDK1蛋白表达对神经胶质瘤患者预后的影响。结果TCGA数据库中641例胶质瘤患者的PDK1蛋白表达结果显示，世界卫生组织（世界卫生组织）Ⅳ级胶质瘤中PDK1蛋白的表达水平（8.86±0.90）高于Ⅱ级（7.24±0.60）和Ⅲ级（7.34±0.80）（P＜0.05），高表达组胶质瘤患者累积生存率显著低于低表达组Pearson相关分析显示，96个基因与PDK1表达密切相关，其中69个基因呈正相关，27个基因负相关。GO分析和KEGG通路分析表明，PDK1参与了许多重要的生物学过程，这些过程与缺氧微环境、对有机环状化合物的反应、对有机氮化合物的反应、cAMP的反应和HIF-1信号通路密切相关。多因素分析表明，年龄（HR=1.579，95%CI:1.085-2.299，P=0.017）、世界卫生组织分级（HR=12.06，95%CI:6.521-2.474，P=0.001）和放疗（HR=0.502，95%CI:3.325-0.775，P=0.002）是神经胶质瘤患者生存的独立影响因素（均P<0.05），可独立用于探讨患者预后。然而，PDK1蛋白的表达并不影响神经胶质瘤患者的预后。结论不同世界卫生组织病理水平的胶质瘤患者PDK1表达不同，主要与缺氧和HIF-1信号通路有关。关键词：胶质瘤；预后；癌症基因组图谱；丙酮酸脱氢酶激酶1

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来源期刊

中华神经外科杂志 Medicine-Surgery

CiteScore

0.10

自引率

0.00%

发文量

10706

期刊介绍： Chinese Journal of Neurosurgery is one of the series of journals organized by the Chinese Medical Association under the supervision of the China Association for Science and Technology. The journal is aimed at neurosurgeons and related researchers, and reports on the leading scientific research results and clinical experience in the field of neurosurgery, as well as the basic theoretical research closely related to neurosurgery.Chinese Journal of Neurosurgery has been included in many famous domestic search organizations, such as China Knowledge Resources Database, China Biomedical Journal Citation Database, Chinese Biomedical Journal Literature Database, China Science Citation Database, China Biomedical Literature Database, China Science and Technology Paper Citation Statistical Analysis Database, and China Science and Technology Journal Full Text Database, Wanfang Data Database of Medical Journals, etc.