Microarray analysis of MRI-defined tissue samples in glioblastoma reveals differences in regional expression of therapeutic targets
Microarray analysis of MRI-defined tissue samples in glioblastoma reveals differences in regional expression of therapeutic targets
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DOI：
10.1097/01.pdm.0000213464.06387.36
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发表时间：
2006-12-01
影响因子：
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通讯作者：
Broaddus, William C.
中科院分区：
文献类型：
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作者：
Van Meter, Timothy;Dumur, Catherine;Broaddus, William C.
微阵列技术在评估癌症组织活检中的分子诊断特征方面已经变得突出起来。为了更好地了解抽样偏差的影响，我们将图像引导的立体定向活检和微阵列技术配对来研究未经治疗的胶质母细胞瘤的肿瘤外围和核心区域的区域内差异。用积分组织病理学评分方法从连续冰冻切片中提取RNA。使用高密度寡核苷酸微阵列(22,283个探针组)进行基因表达分析。使用微阵列套件5.0、基于模型的表达指数和稳健的多阵列分析算法，获得了肿瘤周围样本和核心样本之间差异大于2倍的643个基因(784个探针组)的共识列表。用定量聚合酶链式反应和Western blotting分析验证结果。出现了对胶质母细胞瘤有意义的多个治疗靶点[基质金属蛋白酶，AKT1(v-AKT小鼠胸腺瘤病毒癌基因同源1)，表皮生长因子受体，血管内皮生长因子]的区域表达显著差异，可能影响治疗反应。这项研究表明，胶质母细胞瘤的分子表型在肿瘤内具有重要的区域性差异。
Microarray technologies have come into prominence for the assessment of molecular diagnostic profiles in cancer tissue biopsies. To better understand the effect of sampling bias, we paired image-guided stereotactic biopsy and microarray technology to study regional intratumoral differences in tumor periphery and core regions of untreated glioblastoma. RNA was extracted from serial frozen sections using an integral histopathologic scoring approach. Gene expression analysis was performed using high-density oligonucleotide microarrays (22,283 probe sets). A consensus list of 643 genes (784 probe sets) with greater than 2-fold difference between intraturnoral periphery and core samples was obtained using Microarray Suite 5.0, model-based expression indexes, and robust multiarray analysis algorithms. Results were validated using quantitative polymerase chain reaction and Western blotting analyses. Reproducible profiles emerged, in which multiple therapeutic targets significant to glioblastoma [matrix metalloproteinases, AKT1 (v-akt murine thymoma viral oncogene homolog 1), epidermal growth factor receptor, vascular endothelial growth factor] showed significant differences in regional expression that may affect treatment response. This study Suggests important intratumoral regional differences in the molecular phenotype of glioblastoma.