CENPM在脑胶质瘤中的表达特征、预后价值及其调控肿瘤恶性表型的机制研究OA
Expression characteristics and prognostic value of CENPM,and its mechanisms in regulating malignant phenotypes in glioma
目的:探究着丝粒蛋白M(CENPM)在脑胶质瘤中的表达特征、临床预后价值及其对肿瘤恶性生物学行为的调控机制,为脑胶质瘤的精准治疗提供潜在靶点.方法:基于中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库分析CENPM在胶质瘤中的表达及其与患者临床病理特征和预后的相关性.通过基因本体论(GO)分析、京都基因与基因组百科全书(KEGG)富集分析和单细胞转录组分析探索CENPM的生物学功能和作 用 机 制.WB 法检测 CENPM 在 胶 质瘤细胞(LN-18、LN-229、U-138MG、U-251MG)和正常胶质细胞(HEB)中的表达;构建CENPM敲低细胞后,通过CCK-8、集落形成、Transwell和划痕实验评估恶性表型改变.结果:CENPM在WHO高级别胶质瘤中呈高表达(P<0.05),与肿瘤恶性程度正相关.高表达组患者总体生存期显著短于低表达组(P<0.01),Cox回归证实CENPM是影响胶质瘤患者预后的独立危险因素(P<0.05).功能富集分析结果显示CENPM相关基因主要富集于细胞周期调控、PI3K-Akt 通路和免疫相关过程.单 细 胞分析结果显示CENPM主要在CD8⁺ T细胞高表达,并通过PTN-PTPRZ1/NCL配受体调控细胞通信.体外实验证实CENPM在胶质瘤细胞表达高于正常胶质细胞(LN-18:P<0.01,LN-299:P<0.05);敲低CENPM显著抑制迁移(P<0.05),但增强集落形成,提示其在肿瘤进展中的双重调控作用.结论:CENPM作为胶质瘤独立预后危险因子,通过调控细胞周期、PTN通路和免疫微环境驱动肿瘤进展,其差异化调控机制(抑制迁移、促进增殖)具有潜在的临床转化价值,可作为分子分型和靶向治疗候选标志物.
Objective:To investigate the expression characteristics and clinical prognostic value of centromere protein M(CENPM)in glioma,and its regulatory mechanisms on malignant biological behaviors,providing potential targets for precision therapy in glioma.Methods:Based on the Chinese Glioma Genome Atlas(CGGA)and the Cancer Genome Atlas(TCGA)database,the expression of CENPM in glioma and its correlation with patients'clinicopathological features and prognosis were analyzed.Gene Ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and single-cell transcriptome analysis were performed to explore the biological functions and mechanisms of CENPM.WB was used to detect CENPM expressions in glioma cell lines(LN-18,LN-229,U-138MG,U-251MG)and a normal glial cell line(HEB).After constructing CENPM knockdown cell lines,the alterations in malignant phenotypes were assessed using CCK-8,colony formation,Transwell,and wound healing assays.Results:CENPM was significantly upregulated in WHO high-grade gliomas(P<0.05)and positively correlated with tumor malignancy.Patients in the high-expression group had significantly shorter overall survival than those in the low-expression group(P<0.01),and Cox regression confirmed CENPM as an independent risk factor for glioma prognosis(P<0.05).Functional enrichment analysis showed that CENPM-related genes were primarily enriched in cell cycle regulation,the PI3K-Akt pathway,and immune-related processes.Single-cell analysis indicated that CENPM was primarily highly expressed in CD8⁺ T cells and regulated cell communication through the PTN-PTPRZ1/NCL ligand-receptor pair.In vitro experiments confirmed that CENPM expression was higher in glioma cell lines than in normal glial cells(LN-18:P<0.01,LN-299:P<0.05);knockdown of CENPM significantly inhibited migration(P<0.05)but enhanced colony formation,suggesting its dual regulatory role in tumor progression.Conclusion:CENPM,an independent prognostic risk factor in glioma,drives tumor progression by regulating the cell cycle,the PTN pathway,and immune microenvironment.Its differential regulatory mechanisms(inhibiting migration while promoting proliferation)hold potential clinical translational value and may serve as a candidate marker for molecular subtyping and targeted therapy.
袁浩;张斯玮;王梦玥;孙桥欣;白梓利;陈鹏
西安医学院 基础医学部 生物化学与分子生物学实验中心,陕西 西安 710021西安医学院 基础医学部 生物化学与分子生物学实验中心,陕西 西安 710021西安医学院 基础医学部 生物化学与分子生物学实验中心,陕西 西安 710021西安医学院 基础医学部 生物化学与分子生物学实验中心,陕西 西安 710021西安医学院 基础医学部 生物化学与分子生物学实验中心,陕西 西安 710021西安医学院 基础医学部 生物化学与分子生物学实验中心,陕西 西安 710021
医药卫生
脑胶质瘤着丝粒蛋白M预后增殖PI3K-Akt通路
gliomacentromere protein M(CENPM)prognosisproliferationPI3K-Akt pathway
《中国肿瘤生物治疗杂志》 2026 (4)
418-428,11
陕西省教育厅科学研究计划(23JK0657)西安医学院博士科研启动基金(2023BS33)西安医学院科技能力提升专项计划(2024NLTS026)西安医学院大学生创新训练计划(121525149,121525089)
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