胃癌是我国常见恶性肿瘤,其中肠型胃癌发病率明显高于弥漫型,发生发展缓慢,早期干预可以明显降低死亡率。我们前期发现,定位于核的PTEN(核PTEN)与肠型胃癌患者预后相关,在肠型胃癌发展中可能起重要作用。在此基础上,1.应用组织芯片技术,研究核PTEN及相关蛋白的表达与癌前病变、肠型胃癌患者病理特征及预后的关系;2.应用核PTEN基因过表达的方法,观察胃癌细胞行为和相关信号通路的改变;探讨核PTEN在胃癌中的抑癌调控机制。该项目探讨核PTEN在胃癌细胞中的抑癌调控机制,为掌握肠型胃癌的发生发展机制奠定良好的基础。

Gastric cancer is the one of the most common malignant tumors in our country. The intestinal type gastric cancer incidence was significantly higher than that of diffuse type and developed slowly, early intervention can reduce the mortality of gastric cancer. We find out early that "nuclear PTEN" was related to prognosis of intestinal type gastric cancer patients, and may play an important role in its development. On this basis, ① with the application of tissue microarray, to study the nuclear PTEN expression in patients with gastric cancer and precancerous lesions, pathological feature and prognosis relations; ② with the application of nuclear PTEN gene overexpression methods, to observe the change of biological behavior of gastric cancer cell line, to study the tumor suppressor mechanism of nuclear PTEN in gastric cancer. The project is to elaborate that the tumor suppressor mechanism of nuclear PTEN in gastric cancer cells, to grasp the occurrence and development mechanism of intestinal type gastric cancer.

本课题主要从两方面探讨核PTEN在胃癌细胞中的抑癌调控机制。首先，连续收集北京友谊医院2008 年1 月-2012 年5 月的胃癌患者病例数据；进行电话随访，随访后确定收集83例基本信息齐全，手术标本病理完整，转归明确的患者构建样本库，确认石蜡组织标本，构建组织芯片，进行核PTEN、PI3K等蛋白的免疫组化染色来明确核PTEN等蛋白的表达与胃癌患者临床特征及预后的关系。其次，筛选PTEN 表达低的HGC-27胃癌细胞株，构建PEGFP-NLS-PTEN 载体，转染至HGC-27胃癌细胞，进行细胞凋亡检测，核PTEN过表达组（OE组）细胞凋亡数相比阴性对照组（NC组）差异有统计学意义（P<0.05）。