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LAMA2蛋白在脑胶质瘤中的表达及预后意义

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目的 探索层粘连蛋白亚基α-2(LAMA2)在脑胶质瘤中的表达特征及可能参与的生物学过程,进而挖掘其临床意义。方法 提取中国脑胶质瘤基因组图谱计划(CGGA)mRNA转录组测序数据库中脑胶质瘤患者的临床资料及mRNA测序数据,剔除数据信息有缺失的病例后进行标准化处理,匹配临床和测序数据,提取LAMA2的表达特征。验证组的脑胶质瘤数据选自癌症基因组图谱计划(TCGA)mRNA测序数据库、REMBRANDT mRNA芯片数据库和GSE16011 mRNA芯片数据库。采用Kaplan-Meier生存曲线、Cox单因素和多因素回归分析评价LAMA2在脑胶质瘤患者总生存期和预后中的价值。在CGGA和TCGA 2个数据集里进行基因富集分析并取交集获得LAMA2蛋白相关基因的功能。结果 CGGA325、TCGA及REMBRANDT mRNA芯片数据库中不同级别脑胶质瘤间,LAMA2的表达量在Ⅱ级脑胶质瘤中最低,在Ⅳ级脑胶质瘤中最高,差异均有统计学意义(均P<0。05)。在脑胶质瘤的四分型分析数据中,恶性程度较高的经典型和间质型脑胶质瘤组LAMA2的表达水平高于恶性程度较低的前神经元型和神经元型,差异均有统计学意义(均P<0。01)。在CGGA325、CGGA693、GSE16011和TCGA芯片数据库中,异柠檬酸脱氢酶(IDH)野生型脑胶质瘤中LAMA2的表达水平高于IDH突变型脑胶质瘤,差异有统计学意义(P<0。01)。CGGA325数据库全级别脑胶质瘤和低级别脑胶质瘤中,Kaplan-Meier生存分析显示,LAMA2基因高表达组患者总体生存率均低于低表达组,差异有统计学意义(均P<0。05)。多因素Cox回归分析结果显示,年龄、WHO病理级别、1p19q共缺失状态、LAMA2表达量是脑胶质瘤患者生存期的影响因素(均P<0。05)。GO富集分析显示,LAMA2蛋白与脑胶质瘤细胞的细胞外基质组织、外部封装结构组织、细胞外结构组织、胶原纤维组织、血管发育、血管形态发生、血管生成等生物学过程相关。结论 LAMA2蛋白的表达量与脑胶质瘤恶性程度正相关,可作为脑胶质瘤患者预后判断的指标和潜在治疗靶点。
Expression and prognostic significance of LAMA2 in gliomas
Objective To explore the expression characteristics of laminin subunit alpha-2(LAMA2)in gliomas and the biological processes it may be involved in,so as to tap its clinical significance.Methods Clinical information and RNAseq data of glioma patients in the Chinese Glioma Genome Atlas(CGGA)RNAseq database were extracted.Cases with missing data information were excluded and then standardized,and clinical and sequencing data were matched to extract the expression characteristics of LAMA2.The glioma data of validation group was selected from The Cancer Genome Atlas(TCGA)mRNA sequencing database,the REMBRANDT microarry database,and the GSE16011 microarry database.Kaplan-Meier survival curves,Cox univariate and multivariate regression analyses were used to evaluate the value of LAMA2 in the overall survival and prognosis of glioma patients.Gene enrichment analysis was performed in two datasets,CGGA and TCGA,and intersections were taken to obtain the functions of LAMA2-related genes.Results Between different grades of gliomas in CGGA325,TCGA and REMBRANDT microarry databases,the expression of LAMA2 was the lowest in grade Ⅱ gliomas and the highest in grade Ⅳ gliomas,and the differences were all statistically significant(all P<0.05).In the subtype analysis data of brain gliomas,the expression level of LAMA2 in highly malignant classical and mesenchymal glioma groups was higher than that of less malignant preneuronal and neuronal types,and the differences were all statistically significant(all P<0.01).In CGGA325,CGGA693,GSE16011 and TCGA databases,the expression level of LAMA2 in IDH wild-type gliomas was higher than that in IDH mutant gliomas,and the difference was statistically significant(P<0.01).Kaplan-Meier survival analysis in both full-grade gliomas and low-grade gliomas in the CGGA325 database showed that the overall survival of patients in high-expression group of the LAMA2 gene was worse than that of low-expression group,and the difference was statistically significant(all P<0.05).Multivariate Cox regression analysis showed that age,pathological grade,1p19q co-deletion,and LAMA2 expression were independent influencing factors of survival in patients with primary glioma,and the differences were all statistically significant(all P<0.05).DEG enrichment analysis showed that LAMA2 was associated with biological processes such as extracellular matrix organization,external encapsulated structural organization,extracellular structural organization,collagen fiber organization,vascular development,vascular morphogenesis,and angiogenesis in glioma cells.Conclusions The expression of LAMA2 is positively correlated with the malignancy degree of gliomas,which can be used as a prognostic indicator and potential therapeutic target for patients with primary gliomas.

GliomaLaminin subunit alpha-2Gene expressionPrognosisTargeted therapy

陈婧、李卓群、宁佐君、张克难

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100070 北京市神经外科研究所

神经胶质瘤 层粘连蛋白亚基α-2 基因表达 预后 靶点治疗

2025

神经疾病与精神卫生
齐齐哈尔医学院

神经疾病与精神卫生

影响因子:0.579
ISSN:1009-6574
年,卷(期):2025.25(1)