神经胶质蛋白在胶质母细胞瘤中的表达及其对预后的影响

doi:10.19854/j.cnki.1008-2425.2024.05.0001

立体定向和功能性神经外科杂志 ›› 2024, Vol. 37 ›› Issue (5): 257-261.DOI: 10.19854/j.cnki.1008-2425.2024.05.0001

• 论著 • 下一篇

神经胶质蛋白在胶质母细胞瘤中的表达及其对预后的影响

杨明龙, 伍鹏飞, 牛朝诗

230001 合肥安徽医科大学附属省立医院神经外科(杨明龙,牛朝诗);脑功能与脑疾病安徽省重点实验室(杨明龙,伍鹏飞,牛朝诗);中国科学技术大学附属第一医院神经外科(伍鹏飞,牛朝诗)

收稿日期:2024-10-10 出版日期:2024-10-25 发布日期:2024-12-17
通讯作者: 牛朝诗 niuchaoshi@163.com
基金资助:
中央高校基本科研业务费专项资金资助项目(编号:WK9110000145)

Expression and prognostic implications of GLDN in glioblastoma

Yang Minglong^1,2, Wu Pengfei², Niu Chaoshi^1,2

1. Department of Neurosurgery,Anhui Provincial Hospital Affiliated to Anhui Medical University,Hefei 230001,Anhui,China;
2. Department of Neurosurgery,the First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China

Received:2024-10-10 Online:2024-10-25 Published:2024-12-17
Contact: Niu Chaoshi niuchaoshi@163.com

摘要/Abstract

摘要： 目的探讨神经胶质蛋白(gliomedin,GLDN)在胶质母细胞瘤(glioblastoma,GBM)组织和胶质母细胞瘤细胞系中的表达变化,以及其对患者预后的影响。方法通过对本课题组内的胶质母细胞瘤耐药相关研究中的测序数据进行进一步挖掘分析,从国际数据库GEO中下载收录的GSE113510 mRNA测序数据,筛选出差异表达最明显的基因GLDN;在CGGA数据库中分析原发和复发GBM组织的GLDN表达差异;通过实时荧光定量PCR检测GBM细胞系中的GLDN mRNA水平,Western blot检测其蛋白水平;并使用CGGA和TCGA数据库中的生存分析探讨GLDN的表达与患者预后的关系。结果分析GSE113510数据后发现,GLDN在耐药胶质母细胞瘤细胞系中差异表达最为显著。复发性GBM组织中GLDN的表达量显著高于原发性GBM(P＜0.05)。在耐药细胞系229R、251R、HG7R中,GLDN的表达显著升高(P＜0.05)。生存分析显示,GLDN高表达与患者更差的预后相关,生存时间显著缩短。结论 GLDN在胶质母细胞瘤中高表达,且与耐药性及预后不良密切相关,可能是GBM治疗中的潜在分子靶标。

关键词: 神经胶质蛋白, 胶质母细胞瘤, 耐药性, 生存分析, 分子靶标

Abstract: Objective To investigate the expression changes of GLDN (Gliomedin) in glioblastoma (GBM) tissues and cell lines,and its impact on patient prognosis. Methods By conducting further mining and analysis of sequencing data from previously published studies on glioblastoma multiforme (GBM) drug resistance within our research group,we downloaded the GSE113510 mRNA sequencing data from the international GEO database,GLDN was identified as the gene with the most significant differential expression.The expression differences of GLDN between primary and recurrent GBM tissues were analyzed using the CGGA database.GLDN mRNA levels in GBM cell lines were measured by quantitative real-time PCR,and protein levels were detected by Western blotting.Survival analysis using the CGGA and TCGA databases was conducted to examine the relationship between GLDN expression and patient prognosis. Results Analysis of the GSE113510 dataset revealed that GLDN exhibited the most significant differential expression in drug-resistant GBM cell lines.GLDN expression was significantly higher in recurrent GBM tissues compared to primary GBM tissues (P＜0.05).Additionally,GLDN expression was markedly elevated in drug-resistant cell lines 229R,251R,and HG7R compared to their non-resistant counterparts (P＜0.05).Survival analysis showed that high GLDN expression was associated with poorer patient prognosis,with a significantly shorter survival time. Conclusion GLDN is highly expressed in glioblastoma and is closely associated with drug resistance and poor prognosis.It may serve as a potential therapeutic target in GBM treatment.

Key words: GLDN, glioblastoma, Drug resistance, Survival analysis, Therapeutic target

中图分类号:

R739.41

杨明龙, 伍鹏飞, 牛朝诗. 神经胶质蛋白在胶质母细胞瘤中的表达及其对预后的影响[J]. 立体定向和功能性神经外科杂志, 2024, 37(5): 257-261.

Yang Minglong, Wu Pengfei, Niu Chaoshi. Expression and prognostic implications of GLDN in glioblastoma[J]. Chinese Journal of Stereotactic and Functional Neurosurgery, 2024, 37(5): 257-261.

参考文献

[1] Maluenda J,Manso C,Quebarec L,et al.Mutations in GLDN,Encoding Gliomedin,a critical component of the nodes of ranvier,are responsible for lethal arthrogryposis[J].Am J Hum Genet,2016,99(4):928~933.
[2] Labasque M,Devaux JJ,Leveque C,et al.Fibronectin type III-like domains of neurofascin-186 protein mediate gliomedin binding and its clustering at the developing nodes of Ranvier[J].J Biol Chem,2011,286(49):42426~42434.
[3] Chen H,Yang M,Wang Q,et al.The new identified biomarkers determine sensitivity to immune check-point blockade therapies in melanoma[J].Oncoimmunology,2019,8(8):1608132.
[4] Chen W,Li W,Liu Z,et al.Identification of tumor microenvironment-based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma[J].J Cancer,2022,13(3):877~889.
[5] Cescon M,Rampazzo E,Bresolin S,et al.Collagen VI sustains cell stemness and chemotherapy resistance in glioblastoma[J].Cell Mol Life Sci,2023,80(8):233.
[6] Huang J,Zhang L,Wan D,et al.Extracellular matrix and its therapeutic potential for cancer treatment[J].Signal Transduct Target Ther,2021,6(1):153.
[7] Sohrabi A,Lefebvre A,Harrison MJ,et al.Microenvironmental stiffness induces metabolic reprogramming in glioblastoma[J].Cell Rep,2023,42(10):113175.
[8] Zhao Z,Zhang KN,Wang Q,et al.Chinese Glioma Genome Atlas (CGGA):A comprehensive resource with functional genomic data from Chinese glioma patients[J].Genomics Proteomics Bioinformatics,2021,19(1):1~12.
[9] Collado J,Boland L,Ahrendsen JT,et al.Understanding the glioblastoma tumor microenvironment:leveraging the extracellular matrix to increase immunotherapy efficacy[J].Front Immunol,2024,15:1336476.
[10] Mahaffey BJ,Fowler ZP,Lung Z,et al.The prognostic effect of mechanical,ultrastructural,and ECM signatures in glioblastoma core and rim[J].APL Bioeng,2024,8(3):036101.
[11] Xiao W,Wang S,Zhang R,et al.Bioengineered scaffolds for 3D culture demonstrate extracellular matrix-mediated mechanisms of chemotherapy resistance in glioblastoma[J].Matrix Biol,2020,85-86:128~146.
[12] Xiao W,Zhang R,Sohrabi A,et al.Brain-mimetic 3D culture platforms allow investigation of cooperative effects of extracellular matrix features on therapeutic resistance in glioblastoma[J].Cancer Res,2018,78(5):1358~1370.
[13] Yu Q,Xiao W,Sun S,et al.Extracellular matrix proteins confer cell adhesion-mediated drug resistance through integrin alpha (v) in glioblastoma cells[J].Front Cell Dev Biol,2021,9:616580.
[14] Gao L,Guan Z,Gao P,et al.Cytophaga hutchinsonii gldN,encoding a component of the type IX secretion system,is essential for ion assimilation,cellulose degradation,and cell motility[J].Appl Environ Microbiol,2020,86(11):e00242~20.
[15] Kraft T,Grützmann K,Meinhardt M,et al.Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs[J].Acta Neuropathologica Communications,2024,12(1):67.

神经胶质蛋白在胶质母细胞瘤中的表达及其对预后的影响

Expression and prognostic implications of GLDN in glioblastoma

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王宜兵, 张磊, 陈建军, 常成, 宋国智. 基于术前MRI+3D slicer技术的显微镜下切除术对脑胶质瘤患者肿瘤标志物、神经功能及预后的影响[J]. 立体定向和功能性神经外科杂志, 2024, 37(5): 262-266.
[2]	洪家康, 李陈, 周夏, 戴荣权, 张志超. 多模态影像融合三维重建在垂体瘤术前规划中的应用(附27例临床分析)[J]. 立体定向和功能性神经外科杂志, 2024, 37(5): 308-310.
[3]	牛万祥, 慕茂林, 张宏伟, 计颖, 程传东. 脑胶质瘤患者继发第二原发恶性肿瘤的相关分析[J]. 立体定向和功能性神经外科杂志, 2024, 37(4): 199-204.
[4]	杜蓓, 高凯, 刘常权, 刘英彦. 卡莫司汀结合替莫唑胺通过调节生长因子及其受体水平治疗胶质瘤的作用研究[J]. 立体定向和功能性神经外科杂志, 2024, 37(2): 107-115.
[5]	孟强, 荆江鹏, 李焕发, 刘永, 武昊, 任宇涛, 张佳乐, 张华. 海绵状血管瘤相关性癫痫患者手术疗效的预测因素分析[J]. 立体定向和功能性神经外科杂志, 2024, 37(1): 6-10.
[6]	王国杰, 刘莹, 韩艳华, 任秀娥, 梁日晶. 胶质瘤患者MRI参数Ktrans值和Ve值与血清IL-10、VEGF的交互作用及对脑胶质瘤分级的诊断[J]. 立体定向和功能性神经外科杂志, 2024, 37(1): 11-16.
[7]	王宣之, 李政, 张伟文, 李健基, 姜晓峰, 牛朝诗. 3D打印鼻颅底肿瘤模型在神经外科临床与教学中的应用[J]. 立体定向和功能性神经外科杂志, 2024, 37(1): 17-21.
[8]	陆天宇, 俞天赋, 虞晨, 陈维涛, 倪红斌. 枕骨大孔区脑膜瘤的显微手术治疗体会(附15例临床分析)[J]. 立体定向和功能性神经外科杂志, 2023, 36(6): 354-358.
[9]	周占元, 张国荣. 立体定向放射外科治疗非小细胞肺癌脑转移瘤的挑战与进展[J]. 立体定向和功能性神经外科杂志, 2023, 36(6): 376-381.
[10]	蒋艳, 曾煜, 刘备, 雷科. 脑膜瘤术前MRI特征对术后复发风险的预测价值研究[J]. 立体定向和功能性神经外科杂志, 2023, 36(4): 228-232.
[11]	杜云, 王卫中, 刘梦, 姚萌萌. 异柠檬酸脱氢酶1R132H与同源框C10在脑胶质瘤组织的表达及其临床意义[J]. 立体定向和功能性神经外科杂志, 2023, 36(3): 135-140.
[12]	张照华, 杨丽萍, 钟浩龙, 周铭. 术前锥体束受侵犯程度对胶质瘤患者术后替莫唑胺化疗疗效的影响[J]. 立体定向和功能性神经外科杂志, 2023, 36(3): 141-146.
[13]	左赋兴, 蔡洪庆, 何永昌, 苑青, 万经海. 术中超声引导脑深部肿瘤切除疗效分析[J]. 立体定向和功能性神经外科杂志, 2023, 36(2): 90-94.
[14]	杜云, 王卫中, 刘梦, 姚萌萌. Notch3与TIP30表达对脑胶质瘤患者预后评估价值[J]. 立体定向和功能性神经外科杂志, 2022, 35(5): 273-279.
[15]	陆天宇，虞晨，俞天赋，陈维涛，梁维邦，倪红斌. 神经导航辅助下侧脑室脑膜瘤显微手术切除疗效分析[J]. 立体定向和功能性神经外科杂志, 2022, 35(4): 193-197.