First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, 115 27, Greece.
Br J Cancer. 2013 May 28;108(10):2142-52. doi: 10.1038/bjc.2013.176. Epub 2013 Apr 25.
Sox11 is a transcription factor expressed in foetal and neoplastic brain tissue, including gliomas. It has been shown to suppress the tumourigenicity of glioma stem cells in vivo, thereby being hypothesised to function as a tumour suppressor.
We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival.
Sox11 immunoreactivity was identified in all tumours irrespective of grade, but being correlated with p-STAT-3. Three out of seven cases showed partial Sox11 promoter methylation. In >50% of our cases neoplastic cells coexpressed Sox11 and nestin, a finding further confirmed in primary glioblastoma cell cultures. Furthermore, nestin, c-Met and IDH1-R132H expression differed among grade categories. Cluster analysis identified four groups of patients according to c-Met, nestin and IDH1-R132H expression. The c-Met/nestin high-expressor group displayed a higher Sox11 expression. Sox11 expression was an indicator of favourable prognosis in glioblastomas, which remained in multivariate analysis and validated in an independent set of 72 cases. The c-Met/nestin high-expressor group was marginally with shorter survival in univariate analysis.
We highlight the importance of Sox11 expression as a favourable prognosticator in glioblastomas. c-Met/nestin/IDH1-R132H expression phenotypes recapitulate the molecular subgroups of malignant glioma.
Sox11 是一种在胎儿和肿瘤脑组织中表达的转录因子，包括神经胶质瘤。它已被证明可以在体内抑制神经胶质瘤干细胞的致瘤性，因此被假设为肿瘤抑制因子。
我们研究了 Sox11 在 132 例弥漫性星形细胞瘤中的表达，与调节细胞标志物巢蛋白、c-Met 和 IDH1-R132H 有关，这些标志物已被证明在恶性神经胶质瘤的分子亚群中存在差异表达，以及星形胶质细胞分化的诱导剂，即信号转导和转录激活因子（p-STAT-3）、临床病理特征和生存。
Sox11 免疫反应性在所有肿瘤中均被识别，与 p-STAT-3 相关。在 7 例中有 3 例显示 Sox11 启动子部分甲基化。在我们的病例中，超过 50%的肿瘤细胞共同表达 Sox11 和巢蛋白，这一发现在原发性神经母细胞瘤细胞培养中得到了进一步证实。此外，巢蛋白、c-Met 和 IDH1-R132H 的表达在不同的分级类别中存在差异。聚类分析根据 c-Met、巢蛋白和 IDH1-R132H 的表达将患者分为四组。c-Met/巢蛋白高表达组 Sox11 表达较高。Sox11 表达是胶质母细胞瘤预后良好的指标，在多变量分析中仍然存在，并在 72 例独立病例中得到验证。c-Met/巢蛋白高表达组在单变量分析中具有较短的生存时间。
我们强调 Sox11 表达作为胶质母细胞瘤预后良好的预测因子的重要性。c-Met/巢蛋白/IDH1-R132H 表达表型再现了恶性神经胶质瘤的分子亚群。
