Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1399-408. doi: 10.1158/1055-9965.EPI-09-1213. Epub 2010 May 25.
Insulin-like growth factor (IGF)-binding protein (IGFBP) isoforms have been implicated in the pathogenesis of human neoplasms including glioma. In view of this, we evaluated the expression of IGFBP isoforms (IGFBP-2, -3, and -5) during malignant progression of astrocytoma and their prognostic significance in glioblastoma.
The expression of IGFBP isoforms was analyzed in diffusely infiltrating astrocytomas by real-time quantitative PCR (n = 203) and immunohistochemistry (n = 256). Statistical methods were used to assess their grade-specific expression pattern and mRNA-protein intercorrelation. Survival analyses were done on a uniformly treated, prospective cohort of adult patients with newly diagnosed glioblastoma (n = 136) by using Cox regression models.
The mean transcript levels of IGFBP-2 and -3 were significantly higher in glioblastomas (GBM) relative to anaplastic astrocytoma (AA), diffuse astrocytoma (DA), and controls whereas IGFBP-5 mRNA was higher in GBM relative to AA and controls (P < 0.05). By immunohistochemistry, the mean labeling index of all isoforms was significantly higher in GBM compared with AA, DA, and control (P < 0.05). A strong positive correlation was observed between their respective mRNA and protein expressions (P < 0.01). Multivariate analysis revealed IGFBP-3 expression (hazard ratio, 1.021; P = 0.030) and patient age (hazard ratio, 1.027; P = 0.007) to be associated with shorter survival in glioblastoma.
This study shows the associations of IGFBP-2, -3, and -5 expression with increasing grades of malignancy in astrocytomas. IGFBP-3 is identified as a novel prognostic glioblastoma biomarker. The strong correlation between their mRNA and protein expression patterns suggests their role in the pathogenesis of these tumors.
IGFBP isoforms have emerged as biomarkers with diagnostic and prognostic utility in astrocytomas.
胰岛素样生长因子结合蛋白（IGFBP）同工型已被认为与包括神经胶质瘤在内的人类肿瘤的发病机制有关。有鉴于此，我们评估了 IGFBP 同工型（IGFBP-2、-3 和-5）在星形细胞瘤恶性进展过程中的表达及其在胶质母细胞瘤中的预后意义。
通过实时定量 PCR（n=203）和免疫组织化学（n=256）分析弥漫浸润性星形细胞瘤中 IGFBP 同工型的表达。使用统计方法评估它们的分级特异性表达模式和 mRNA-蛋白相互关系。通过 Cox 回归模型对一组接受统一治疗的新诊断胶质母细胞瘤成人患者（n=136）进行生存分析。
IGFBP-2 和-3 的平均转录水平在胶质母细胞瘤（GBM）中明显高于间变性星形细胞瘤（AA）、弥漫性星形细胞瘤（DA）和对照组，而 IGFBP-5mRNA 在 GBM 中高于 AA 和对照组（P<0.05）。通过免疫组织化学，所有同工型的平均标记指数在 GBM 中均明显高于 AA、DA 和对照组（P<0.05）。观察到它们各自的 mRNA 和蛋白质表达之间存在强烈的正相关（P<0.01）。多变量分析显示 IGFBP-3 表达（风险比，1.021；P=0.030）和患者年龄（风险比，1.027；P=0.007）与胶质母细胞瘤患者的生存时间较短有关。
本研究表明 IGFBP-2、-3 和-5 的表达与星形细胞瘤恶性程度的增加有关。IGFBP-3 被鉴定为胶质母细胞瘤的新型预后生物标志物。它们的 mRNA 和蛋白质表达模式之间的强相关性表明它们在这些肿瘤发病机制中的作用。
IGFBP 同工型已成为星形细胞瘤具有诊断和预后效用的生物标志物。
