The exploration of novel therapeutic target in gastric cancer by comprehensive tyrosine-kinase analysis

我们分析了胃癌中的全面基因表达，以探索与肿瘤发生，特别是腹膜转移相关的新的酪氨酸激酶。然后鉴定了新的和已知的酪氨酸激酶：KSR1和MEK，Her2和FGFR1。KSR1是一种酪氨酸激酶，是RAS途径的正向调节因子，与细胞的运动、侵袭和腹膜扩散有关。通过相关分析和基因表达分析，确定FOXM1、DOK2和REGIV分别为MEK、Her2和FGFR1酪氨酸激酶的下游分子。结果表明，这些分子与预后、腹膜扩散和抗癌药物的敏感性有关，这一结果可能使我们能够阐明与胃癌生物学特性相关的信号转导机制，开发新型的分子靶向药物。

We analyzed the comprehensive gene expression in gastric cancer to explore the novel tyrosine-kinase related to the development of cancer, especially peritoneal dissemination. Then the novel and well-known tyrosine-kinases; KSR1 and MEK, Her2 and FGFR1 were identified. KSR1 is a tyrosine-kinase that functions as positive regulator of Ras pathway, and associated with the cell motility, invasion and peritoneal dissemination. FOXM1, DOK2 and REGIV are identified as the downstream molecules of the tyrosine-kinases, MEK, Her2 and FGFR1, respectively in consequence of the analysis of the correlativity between the pathways of these tyrosine-kinases and gene expression analysis. It was shown that these molecules related with the prognosis, peritoneal dissemination and the sensitivity of anticancer drug.This result may enable us to elucidate the signaling related to the biological character of gastric cancer and develop the novel molecular-targeted agent.