[1]黄冠又,张欣,甘鸿川,等.胶质母细胞瘤氧化应激相关基因的表达分析[J].中国临床神经外科杂志,2023,28(04):259-262.[doi:10.13798/j.issn.1009-153X.2023.04.010]
　HUANG Guan-you,ZHANG Xin,GAN Hong-chuan,et al.Expression analysis of oxidative stress-related genes in glioblastoma based on bioinformatics analysis[J].,2023,28(04):259-262.[doi:10.13798/j.issn.1009-153X.2023.04.010]
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胶质母细胞瘤氧化应激相关基因的表达分析()
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《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
28
期数:
2023年04期
页码:
259-262
栏目:
论著
出版日期:
2023-04-30

文章信息/Info

Title:
Expression analysis of oxidative stress-related genes in glioblastoma based on bioinformatics analysis
文章编号:
1009-153X（2023）04-0259-04
作者:
黄冠又; 张欣; 甘鸿川; 郝淑煜; 吴震
550081贵阳，贵州医科大学附属金阳医院神经外科（黄冠又、张欣、甘鸿川）；100070北京，首都医科大学附属北京天坛医院神经外科（郝淑煜、吴震）
Author(s):
HUANG Guan-you1;  ZHANG Xin1;  GAN Hong-chuan1;  HAO Shu-yu2;  WU Zhen2
1.Department of Neurosurgery, Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang 550081, China; 2.Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
关键词:
胶质母细胞瘤; 氧化应激; 基因表达
Keywords:
Glioblastoma;  Oxidative stress;  Gene expression;  Bioinformatics analysis
分类号:
A
DOI:
10.13798/j.issn.1009-153X.2023.04.010
文献标志码:
R739.41;Q786
摘要:
目的 探讨胶质母细胞瘤（GBM）氧化应激关键基因的表达变化。方法 从UCSC Xena数据库下载167例GBM基因表达谱数据（TCGA-GBM），从GeneCards数据库下载氧化应激基因集（168个氧化应激相关基因）；通过富集分析确定差异表达基因（DEGs），建立蛋白-蛋白相互作用（PPI）网络识别关键基因，利用Spearman相关系数对免疫因子和免疫检查点与关键基因进行相关性分析。结果 鉴定出两种与氧化应激相关的GBM分子亚型（Cluster1和Cluster2），Cluster1型GBM生存期明显高于Cluster2型（P<0.05）。共筛选出54个DEGs，在细胞因子/趋化因子相关功能中显著富集。PPI网络鉴定出10个关键基因，即CSF2、CSF3、CCL7、LCN2、CXCL6、MMP8、CCR8、TNFSF11、IL22RA2和ORM1。大多数免疫因子和免疫检查点与关键基因呈正相关。结论 本文基于氧化应激相关基因将GBM划分为两个亚型，并且筛选出10个氧化应激基因，可能在GBM的发生、发展过程中起重要作用，也可能对GBM预后评估具有一定的价值。
Abstract:
Objective To investigate the expression changes of key genes related to oxidative stress in glioblastomas (GBM). Methods The transcriptome data of GBM (167 GBM patients) were downloaded from Cancer Genome Atlas (TCGA) database, and the oxidative stress gene set (168 oxidative stress-related genes) was downloaded from GeneCards database. The function of differentially expressed genes (DEGs) was determined by GO and KEGG enrichment analyses, and the protein-protein interaction (PPI) network was established to identify key genes. Spearman correlation coefficient was used to analyze the correlation between immune factors and checkpoints and key genes. Results Two molecular subtypes related to oxidative stress of GBM were identified (Cluster1 and Cluster2), and the survival time of Cluster1 was significantly longer than Cluster2 (P<0.05). Fifty-four DEGs related to oxidative stress were identified and they were significantly enriched in cytokine/chemokine related functions. Ten hub genes were identified by PPI network, namely CSF2, CSF3, CCL7, LCN2, CXCL6, MMP8, CCR8, TNFSF11, IL22RA2 and ORM1. Most immune factors and immune checkpoints were positively correlated with the 10 hub genes. Conclusions Our results suggest GBM could be divided into two subtypes based on oxidative stress-related genes. Ten oxidative stress genes were screened out, which may play an important role in the tumorigenesis and development of GBM, and may also have a certain value for the prognosis assessment of GBM patients.

参考文献/References:

[1]胡峻龙，赵世光. 替莫唑胺治疗脑胶质瘤的新进展[J]. 中国临床神经外科杂志，2021，26（8）：647-649.
[2]Tan AC, Ashley DM, López GY, et al. Management of glioblastoma: state of the art and future directions [J]. CA Cancer J Clin, 2020, 70(4): 299.
[3]Bahadur S, Sahu AK, Baghel P, et al. Current promising treatment strategy for glioblastoma multiform: a review [J]. Oncol Rev, 2019, 13(2): 417.
[4]Ostrowski RP, Pucko EB. Harnessing oxidative stress for anti-glioma therapy [J]. Neurochem Int, 2022, 154: 105281.
[5]Wu L, Wang F, Xu J, et al. PTPN2 induced by inflammatory response and oxidative stress contributed to glioma progression [J]. J Cell Biochem, 2019, 120(11): 19044.
[6]Lu D, Yang N, Wang S, et al. Identifying the predictive role of oxidative stress genes in the prognosis of glioma patients [J]. Med Sci Monit, 2021, 27: e934161.
[7]Da Ros M, De Gregorio V, Iorio AL, et al. Glioblastoma chemoresistance: the double play by microenvironment and blood-brain barrier [J]. Int J Mol Sci, 2018, 19(10): 2879.
[8]Yeo ECF, Brown MP, Gargett T, et al. The role of cytokines and chemokines in shaping the immune microenvironment of glioblastoma: implications for immunotherapy [J]. Cells, 2021, 10(3): 607.
[9]Chang AL, Miska J, Wainwright DA, et al. CCL2 produced by the glioma microenvironment is essential for the recruitment of regulatory T cells and myeloid-derived suppressor cells [J]. Cancer Res, 2016, 76(19): 5671.
[10]Pan Y, Smithson LJ, Ma Y, et al. Ccl5 establishes an auto-crine high-grade glioma growth regulatory circuit critical for mesenchymal glioblastoma survival [J]. Oncotarget, 2017, 8(20): 32977.
[11]Giordano FA, Link B, Glas M, et al. Targeting the post-irradiation tumor microenvironment in glioblastoma via inhibition of CXCL12 [J]. Cancers (Basel), 2019, 11(3): 272.
[12]Wang Q, He Z, Huang M, et al. Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α [J]. Nat Commun, 2018, 9(1): 559.
[13]Frei K, Gramatzki D, Tritschler I, et al. Transforming growth factor-β pathway activity in glioblastoma [J]. Oncotarget, 2015, 6(8): 5963.
[14]Sielska M, Przanowski P, Pasierbińska M, et al. Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas [J]. Br J Cancer, 2020, 123(3): 438.
[15]Gao Y, Zhang E, Liu B, et al. Integrated analysis identified core signal pathways and hypoxic characteristics of human glioblastoma [J]. J Cell Mol Med, 2019, 23(9): 6228.
[16]Zhu Z, Zhang X, Yu Z, et al. Correlation of Tim-3 expression with chemokine levels for predicting the prognosis of patients with glioblastoma [J]. J Neuroimmunol, 2021, 355: 577575.
[17]Hsieh YH, Tsai JP, Yu CL, et al. Overexpression of lipoca-lin-2 inhibits proliferation and invasiveness of human glioblastoma multiforme cells by activating ERK targeting Cathepsin D expression [J]. Biology (Basel), 2021, 10: 390.
[18]Widodo SS, Dinevska M, Furst LM, et al. IL-10 in glioma[J]. Br J Cancer, 2021, 125(11): 1466.
[19]Schwartzbaum JA, Xiao Y, Liu Y, et al. Inherited variation in immune genes and pathways and glioblastoma risk [J]. Carcinogenesis, 2010, 31(10): 1770.
[20]Urbantat RM, Vajkoczy P, Brandenburg S. Advances in chemokine signaling pathways as therapeutic targets in glioblastoma [J]. Cancers (Basel), 2021, 13(12): 2983.

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备注/Memo

备注/Memo:
（2022-11-19收稿，2023-01-12修回）
基金项目：国家自然科学基金（81672506；81872052）；贵州省卫健委科学技术基金（gzwkj2022-348）
通讯作者：吴　震，E-mail：wuzhen1966@aliyun.com
更新日期/Last Update: 2022-04-30