Lundberg Laboratory for Cancer Research, Department of Pathology, Sahlgrenska Academy at The University of Gothenburg, Göteborg, Sweden.
Int J Cancer. 2011 Sep 1;129(5):1149-61. doi: 10.1002/ijc.25755. Epub 2011 Jan 7.
In gastrointestinal stromal tumors (GISTs), KIT exon 11 deletions are associated with poor prognosis. The aim of this study was to determine the gene expression profiles of GISTs carrying KIT exon 11 deletions and to identify genes associated with poor prognosis. Expression profiling was performed on nine tumors with KIT exon 11 deletions and 7 without KIT exon 11 mutations using oligonucleotide microarrays. In addition, gene expression profiles for 35 GISTs were analyzed by meta-analysis. Expression of CD133 (prominin-1) protein was examined by tissue microarray (TMA) analysis of 204 GISTs from a population-based study in western Sweden. Survival analysis was performed on patients subjected to R0 resection (n=180) using the Cox proportional hazards model. Gene expression profiling, meta-analysis, and qPCR showed up regulation of CD133 in GISTs carrying KIT exon 11 deletions. Immunohistochemical analysis on TMA confirmed CD133 expression in 28% of all tumors. CD133 positivity was more frequent in gastric GISTs (48%) than in small intestinal GISTs (4%). CD133 positivity was also more frequent in GISTs with KIT exon 11 mutations (41%) than in tumors with mutations in KIT exon 9, platelet-derived growth factor receptor α (PDGFRA), or wild-type tumors (0-17%). Univariate survival analysis showed a significant correlation between the presence of CD133 protein and shorter overall survival (hazard ratio=2.23, p=0.027). Multivariate analysis showed that CD133 provided additional information on patient survival compared to age, sex, National Institutes of Health (NIH) risk group and mutational status. CD133 is expressed in a subset of predominantly gastric GISTs with KIT exon 11 mutations and poor prognosis.
在胃肠道间质瘤（GIST）中，KIT 外显子 11 缺失与不良预后相关。本研究旨在确定携带 KIT 外显子 11 缺失的 GIST 的基因表达谱，并鉴定与不良预后相关的基因。使用寡核苷酸微阵列对 9 例携带 KIT 外显子 11 缺失的肿瘤和 7 例无 KIT 外显子 11 突变的肿瘤进行了表达谱分析。此外，还通过荟萃分析分析了 35 例 GIST 的基因表达谱。通过在瑞典西部进行的一项基于人群的研究的组织微阵列（TMA）分析了 204 例 GIST 中 CD133（prominin-1）蛋白的表达。对接受 R0 切除的患者（n=180）进行了 Cox 比例风险模型的生存分析。基因表达谱分析、荟萃分析和 qPCR 显示携带 KIT 外显子 11 缺失的 GIST 中 CD133 上调。TMA 的免疫组织化学分析证实所有肿瘤中有 28%表达 CD133。胃 GIST（48%）中 CD133 阳性率高于小肠 GIST（4%）。KIT 外显子 11 突变的 GIST 中 CD133 阳性率（41%）也高于 KIT 外显子 9、血小板衍生生长因子受体α（PDGFRA）或野生型肿瘤（0-17%）的肿瘤。单因素生存分析显示 CD133 蛋白的存在与总生存期较短有显著相关性（风险比=2.23，p=0.027）。多因素分析显示，与年龄、性别、美国国立卫生研究院（NIH）危险组和突变状态相比，CD133 为患者的生存提供了额外的信息。CD133 在一组主要为胃 GIST 中表达，这些肿瘤具有 KIT 外显子 11 突变和不良预后。
