Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Cancer Sci. 2011 Apr;102(4):883-9. doi: 10.1111/j.1349-7006.2011.01872.x. Epub 2011 Feb 24.
Although the main cause of gastrointestinal stromal tumor (GIST) is gain-of-function mutations in the c-kit gene in the interstitial cells of Cajal, concomitant genetic or epigenetic changes other than c-kit appear to occur in the development of metastasis. We sought to identify the genes involved in the metastatic process of gastric GIST. Microarray analysis was performed to compare gene expressions between three gastric GIST and four metastatic liver GIST. Expression levels were higher for 165 genes and lower for 146 genes in metastatic liver GIST. The upregulation of five oncogenes and downregulation of four tumor suppressor genes including versican and CD9 were confirmed by quantitative reverse transcriptional PCR. Immunohistochemistry in 117 GIST revealed that protein levels of versican and CD9 were higher and lower, respectively, in metastatic GIST. High expression of versican and low expression of CD9 in 104 primary gastric GIST correlated with poor disease-free survival (P = 0.0078 and P = 0.0018). In addition to the c-kit gene mutation, genetic or epigenetic changes other than c-kit play important roles in the metastatic process. In particular, versican and CD9 are potential prognostic markers in gastric GIST.
虽然胃肠道间质瘤（GIST）的主要病因是 Cajal 间质细胞中 c-kit 基因的功能获得性突变，但在转移的发生过程中似乎除了 c-kit 之外还存在其他基因或表观遗传变化。我们试图确定与胃 GIST 转移过程相关的基因。我们对三例胃 GIST 和四例肝转移 GIST 进行了基因芯片分析，以比较基因表达。肝转移 GIST 中 165 个基因的表达水平升高，146 个基因的表达水平降低。定量逆转录 PCR 证实了五个癌基因的上调和四个肿瘤抑制基因（包括 versican 和 CD9）的下调。对 117 例 GIST 的免疫组化分析表明，转移性 GIST 中 versican 的蛋白水平升高，而 CD9 的蛋白水平降低。在 104 例原发性胃 GIST 中，versican 表达水平高和 CD9 表达水平低与无病生存时间较差相关（P = 0.0078 和 P = 0.0018）。除了 c-kit 基因突变外，c-kit 之外的遗传或表观遗传变化在转移过程中也发挥着重要作用。特别是，versican 和 CD9 是胃 GIST 的潜在预后标志物。
