Expression and prognostic implications of GLDN in glioblastoma

doi:10.19854/j.cnki.1008-2425.2024.05.0001

Abstract

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

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

CLC Number:

R739.41

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.

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.

References

[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.