LAMA2蛋白在脑胶质瘤中的表达及预后意义
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国家自然科学基金 (82103623)


Expression and prognostic significance of LAMA2 in gliomas
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    摘要:

    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。

    Abstract:

    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.

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陈婧,李卓群,宁佐君,张克难. LAMA2蛋白在脑胶质瘤中的表达及预后意义[J].神经疾病与精神卫生,2025,(1):41-47
DOI :10.3969/j. issn.1009-6574.2025.01.006.

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  • 在线发布日期: 2025-01-20