Table1_COMMD4 is a novel prognostic biomarker and relates to potential drug resistance mechanism in glioma.XLSX

Background: Glioma as the most frequently discovered tumor affecting the brain shows significant morbidity and fatality rates with unfavorable prognosis. There is an urgent need to find novel therapeutic targets to overcome the low chemotherapeutic efficacy of glioma. This research examined whether the copper-metabolism-domain protein, COMMD4, had predictive and therapeutic significance in glioma.
Methods: Using the freely accessible CGGA (The Chinese Glioma Atlas) and TCGA (The Cancer Genome Atlas) databases, we examined the function of COMMD4 in GBM and LGG. CIBERSORT and TIMER were utilized to assess the associations between COMMD4 and immune cells. The Gene Set Enrichment Analysis (GSEA) was employed to examine the functional data. Furthermore, the link between COMMD4 expression and predicted treatment response was evaluated via CellMiner Cross-Database. Meanwhile, qRT-PCR was conducted to examine COMMD4 expression in human glioma. Finally, Migration and invasion of glioma cells (U-87, U-251) were assessed using transwell assays. R was used to analyze the statistical data.
Results: According to our findings, COMMD4 expression level was higher in patients having grade-dependent glioma who also showed an unfavorable prognosis. Furthermore, qRT-PCR confirmed the high expression of COMMD4 in glioma tissues and cells. Additionally, using integrated correlation analysis, we acquired significant prognostic findings between isocitrate dehydrogenase 1(IDH1) and COMMD4. Meanwhile, a link between COMMD4 and many tumor-infiltrating immune cells was observed. GSEA and drug response analysis revealed the potential mechanism of COMMD4 in drug resistance of glioma.
Conclusion: The current findings validated COMMD4 as a novel biological marker, which might offer insights into the possible drug resistance mechanisms and the impact of the immune microenvironment on glioma. COMMD4 might be used to predict glioma prognosis.

背景：胶质瘤是最常见的脑部原发肿瘤，具有较高的发病率与病死率，且预后不良。目前亟需挖掘新型治疗靶点，以改善胶质瘤化疗疗效低下的困境。本研究旨在探讨铜代谢结构域蛋白COMMD4（copper-metabolism-domain protein）在胶质瘤中是否具有预测及治疗价值。方法：本研究借助公开可获取的中国胶质瘤图谱（Chinese Glioma Atlas, CGGA）与癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库，分析COMMD4在胶质母细胞瘤（Glioblastoma, GBM）及低级别胶质瘤（Low-grade Glioma, LGG）中的表达与功能。采用CIBERSORT与TIMER工具评估COMMD4与免疫细胞的相关性；通过基因集富集分析（Gene Set Enrichment Analysis, GSEA）探究其潜在功能通路。此外，利用CellMiner交叉数据库分析COMMD4表达与化疗响应预测值之间的关联。同时，采用实时定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）检测人胶质瘤组织中COMMD4的表达水平；最后通过Transwell实验检测胶质瘤细胞（U-87、U-251）的迁移与侵袭能力。所有统计数据均采用R语言进行分析。结果：本研究结果显示，恶性程度分级相关的胶质瘤患者中，COMMD4表达水平升高且预后不良。实时定量聚合酶链反应验证了胶质瘤组织与细胞中COMMD4的高表达。此外，通过整合相关性分析，本研究发现异柠檬酸脱氢酶1（isocitrate dehydrogenase 1, IDH1）与COMMD4之间存在显著的预后相关关联。同时，COMMD4的表达与多种肿瘤浸润免疫细胞呈显著相关性。基因集富集分析与药物响应分析揭示了COMMD4参与胶质瘤耐药的潜在分子机制。结论：本研究证实COMMD4可作为新型生物学标志物，为阐明胶质瘤耐药机制及免疫微环境对胶质瘤的影响提供理论依据。同时，COMMD4有望用于预测胶质瘤患者的预后情况。