Altered expression of immune defense genes in pilocytic astrocytomas
Altered expression of immune defense genes in pilocytic astrocytomas
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DOI：
10.1097/01.jnen.0000183345.19447.8e
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发表时间：
2005-10-01
影响因子：
3.2
通讯作者：
Ohgaki, H
中科院分区：
文献类型：
--
作者：
Huang, H;Hara, A;Ohgaki, H
毛细胞性星形细胞瘤（WHO 1级）是一种局限性、生长缓慢的良性星形细胞瘤，最常发生在小脑半球和中线结构，主要发生在儿童和青少年。与成人弥漫性浸润性胶质瘤（如11级星形细胞瘤、少突胶质细胞瘤）相比，毛细胞性星形细胞瘤患者在手术干预后的生存率非常高。为了寻找其良性生物学行为的潜在分子机制，我们通过cDNA阵列分析比较了毛细胞型星形细胞瘤（8例）与正常小脑（4例），低级别星形细胞瘤（WHO分级11; 15例）和少突胶质细胞瘤（WHO分级11; 17例）的基因表达谱。相对于正常小脑、11级星形细胞瘤和少突胶质细胞瘤，许多免疫系统相关基因如HLA-DR α、HLA-DPB 1、HLA-DQB 1、IgG 3、IgGK、FCER 1G、A2 M、FCRN、1FI-56 K和DAP 12在毛细胞星形细胞瘤中上调。在毛细胞性星形细胞瘤中表达水平高于11级星形细胞瘤和少突胶质细胞瘤的基因包括HLA-DR α、HLA-DPA 1、HLA-DPB 1、HLA-DQB 1、A2 M、TIMP 1、TIMP 2、CDKN 1A和SOCS 3，而表达水平较低的基因包括EGFR和PDGFRA。使用整组1176个基因的层次聚类分析将毛细胞型星形细胞瘤与11级星形细胞瘤和少突胶质细胞瘤区分开。聚类分析使用选定的基因亚组的基础上，他们的分子功能显示，免疫系统相关的基因（75个基因）或细胞粘附，迁移和血管生成相关的基因（69个基因）显示出类似的权力，整个基因集毛细胞星形细胞瘤从弥漫性浸润低级别胶质瘤的分离。免疫组织化学显示，HLA-DRa在毛细胞星形细胞瘤的肿瘤细胞中弥漫表达，而在少突胶质细胞瘤中，表达仅限于分散的反应性星形细胞。这些结果表明，毛细胞型星形细胞瘤的基因表达谱显着不同的弥漫性浸润性低级别胶质瘤，其良性生物学行为可能与免疫防御相关基因的上调。
Pilocytic astrocytoma (WHO grade 1) is a circumscribed, slowly growing, benign astrocytoma that most frequently develops in the cerebellar hemispheres and in midline structures and occurs predominantly in childhood and adolescence. In contrast to diffusely infiltrating gliomas in adults (e.g. grade 11 astrocytomas, oligodendrogliomas), survival of patients with pilocytic astrocytoma is excellent after surgical intervention. To search for potential molecular mechanisms underlying its benign biologic behavior, we compared gene expression profiles of pilocytic astrocytomas (8 cases) with those of normal cerebellum (4 cases), low-grade astrocytomas (WHO grade 11; 15 cases), and oligodendrogliomas (WHO grade 11; 17 cases) by cDNA array analysis. A number of immune system-related genes such as HLA-DR alpha, HLA-DPB 1, HLA-DQB1, IgG3, IgGK, FCER1G, A2M, FCRN, 1FI-56K, and DAP12 were upregulated in pilocytic astrocytomas relative to normal cerebellum, grade 11 astrocytomas, and oligodendrogliomas. Genes expressed at higher levels in pilocytic astrocytomas than in grade 11 astrocytomas and oligodendrogliomas include HLA-DR alpha, HLA-DPA1 HLA-DPB1, HLA-DQB1, A2M, TIMP1, TIMP2, CDKN1A, and SOCS3 and those expressed at lower levels include EGFR and PDGFRA. Hierarchical clustering analysis using the entire set of 1176 genes distinguished pilocytic astrocytomas from grade 11 astrocytomas and oligodendrogliomas. Clustering analysis using selected subgroups of genes based on their molecular functions revealed that immune system-related genes (75 genes) or cell adhesion, migration, and angiogenesis-related genes (69 genes) showed similar power to the entire gene set for separation of pilocytic astrocytomas from diffusely infiltrating low-grade gliomas. Immunohistochemistry revealed that HLA-DRa is expressed diffusely in neoplastic cells in pilocytic astrocytomas, whereas in oligodendrogliomas, expression was limited to scattered reactive astrocytes. These results suggest that gene expression profiles of pilocytic astrocytomas differ significantly from those of diffusely infiltrating low-grade gliomas and that their benign biologic behavior may be related to upregulation of immune defense-associated genes.