Liang Yu, Bollen Andrew W, Nicholas M Kelly, Gupta Nalin
Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, CA 94143, USA.
BMC Clin Pathol. 2005 Jul 15;5:6. doi: 10.1186/1472-6890-5-6.
Oligodendroglioma (ODG) and oligoastrocytoma (OAC) are diffusely infiltrating primary brain tumors whose pathogenesis remains unclear. We previously identified a group of genes whose expression was inversely correlated with survival in a cohort of patients with glioblastoma (GBM), and some of these genes are also reportedly expressed in ODG and OAC. We examined the expression patterns and localization of these survival-associated genes in ODG and OAC in order to analyze their possible roles in the oncogenesis of these two tumor types.
We used UniGene libraries derived from GBM and ODG specimens to examine the expression levels of the transcripts for each of the 50 GBM survival-associated genes. We used immunohistochemistry and cDNA microarrays to examine expression of selected survival-associated genes and Id4, a gene believed to control the timing of oligodendrocyte development. The expression of FABP7 and Id4 and the survival of patients with ODG and OAC were also analyzed.
Transcripts of most survival-associated genes as well as Id4 were present in both GBM and ODG tumors, whereas protein expression of Id4 and one of the survival-associated genes, brain-type fatty acid-binding protein (FABP7), was present in cells with astrocytic features, including reactive and neoplastic astrocytes, but not in neoplastic oligodendrocytes. Id4 was co-expressed with FABP7 in microgemistocytes in ODG and in neoplastic astrocytes in OAC. Id4 and FABP7 expression, however, did not correlate with the clinical outcome of patients with ODG or OAC tumors.
Expression of Id4 and some of our previously identified GBM survival-associated genes is present in developing or mature oligodendrocytes. However, protein expression of Id4 and FABP7 in GBM, ODG, and OAC suggests that this group of functionally important genes might demonstrate two patterns of expression in these glioma subtypes: one group is universally expressed in glioma cells, and the other group of genes is expressed primarily in neoplastic astrocytes but not in neoplastic oligodendrocytes. Differential protein expression of these two groups of genes in ODG and OAC may be related to the cellular origins and the histological features of the neoplastic cells.
少突胶质细胞瘤(ODG)和少突星形细胞瘤(OAC)是弥漫性浸润性原发性脑肿瘤,其发病机制尚不清楚。我们之前在一组胶质母细胞瘤(GBM)患者中鉴定出一组基因,其表达与生存呈负相关,据报道其中一些基因也在ODG和OAC中表达。我们检测了这些生存相关基因在ODG和OAC中的表达模式和定位,以分析它们在这两种肿瘤类型发生过程中的可能作用。
我们使用来自GBM和ODG标本的UniGene文库检测50个GBM生存相关基因各自转录本的表达水平。我们使用免疫组织化学和cDNA微阵列检测选定的生存相关基因以及Id4(一个被认为控制少突胶质细胞发育时间的基因)的表达。还分析了ODG和OAC患者中FABP7和Id4的表达以及患者的生存情况。
大多数生存相关基因以及Id4的转录本在GBM和ODG肿瘤中均存在,而Id4和一个生存相关基因脑型脂肪酸结合蛋白(FABP7)的蛋白表达存在于具有星形细胞特征的细胞中,包括反应性和肿瘤性星形胶质细胞,但不存在于肿瘤性少突胶质细胞中。在ODG的小胶质细胞样细胞和OAC的肿瘤性星形胶质细胞中,Id4与FABP7共表达。然而,Id4和FABP7的表达与ODG或OAC肿瘤患者的临床结局无关。
Id4和我们之前鉴定的一些GBM生存相关基因在发育中的或成熟的少突胶质细胞中表达。然而,Id4和FABP7在GBM、ODG和OAC中的蛋白表达表明,这组功能重要的基因在这些胶质瘤亚型中可能表现出两种表达模式:一组在胶质瘤细胞中普遍表达,另一组基因主要在肿瘤性星形胶质细胞中表达,而不在肿瘤性少突胶质细胞中表达。这两组基因在ODG和OAC中的差异蛋白表达可能与肿瘤细胞的细胞起源和组织学特征有关。