Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location and poor prognosis
Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location and poor prognosis
复制标题
DOI：
10.1002/ijc.25755
复制
发表时间：
2011-09-01
影响因子：
6.4
通讯作者：
Nilsson, Ola
中科院分区：
文献类型：
--
作者：
Arne, Gabriella;Kristiansson, Erik;Nilsson, Ola
在胃肠道间质瘤（GIST）中，KIT外显子11缺失与预后不良相关。本研究的目的是确定携带KIT外显子11缺失的GIST的基因表达谱，并确定与预后不良相关的基因。使用寡核苷酸微阵列对9个KIT外显子11缺失的肿瘤和7个无KIT外显子11突变的肿瘤进行表达谱分析。此外，35个GIST的基因表达谱进行了荟萃分析。通过组织微阵列（TMA）分析来自瑞典西部人群研究的204例GIST，检测CD 133（CD 133 -1）蛋白的表达。使用考克斯比例风险模型对接受R 0切除术的患者（n = 180）进行生存分析。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CD 133的调节上调。TMA的免疫组织化学分析证实了28%的肿瘤表达CD 133。CD 133阳性率在胃GIST中（48%）高于小肠GIST（4%）。CD 133阳性在KIT外显子11突变的GIST中（41%）也比KIT外显子9、血小板衍生生长因子受体α（PDGFRA）或野生型肿瘤中（0-17%）更常见。单变量生存分析显示CD 133蛋白的存在与较短的总生存期之间存在显著相关性（风险比= 2.23，p = 0.027）。多变量分析显示，与年龄、性别、美国国立卫生研究院（NIH）风险组和突变状态相比，CD 133提供了关于患者生存的额外信息。CD 133在主要为胃GIST的亚组中表达，其具有KIT外显子11突变和不良预后。
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 alpha (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.