Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, the People's Republic of China.
BMC Cancer. 2012 Feb 1;12:50. doi: 10.1186/1471-2407-12-50.
The phosphoinositide 3-kinase (PI3K)/Akt pathway plays a fundamental role in cell proliferation and survival in human tumorigenesis, including gastric cancer. PIK3CA mutations and amplification are two major causes of overactivation of this pathway in human cancers. However, until this work, there was no sound investigation on the association of PIK3CA mutations and amplification with clinical outcome in gastric cancer, particularly the latter.
Using direct sequencing and real-time quantitative PCR, we examined PIK3CA mutations and amplification, and their association with clinicopathological characteristics and clinical outcome of gastric cancer patients.
PIK3CA mutations and amplification were found in 8/113 (7.1%) and 88/131 (67%) gastric cancer patients, respectively. PIK3CA amplification was closely associated with increased phosphorylated Akt (p-Akt) level. No relationship was found between PIK3CA mutations and clinicopathological characteristics and clinical outcome in gastric cancer. PIK3CA amplification was significantly positively associated with cancer-related death. Importantly, Kaplan-Meier survival curves revealed that the patients with PIK3CA amplification had significantly shorter survival times than the patients without PIK3CA amplification.
Our data showed that PIK3CA mutations were not common, but its amplification was very common in gastric cancer and may be a major mechanism in activating the PI3K/Akt pathway in gastric cancer. Importantly, Kaplan-Meier survival curves revealed that PIK3CA amplification was significantly positively associated with poor survival of gastric cancer patients. Collectively, the PI3K/Akt signaling pathway may be an effective therapeutic target in gastric cancer.
磷酸肌醇 3-激酶（PI3K）/Akt 途径在人类肿瘤发生中，包括胃癌的细胞增殖和存活中起着基本作用。PIK3CA 突变和扩增是该途径在人类癌症中过度激活的两个主要原因。然而，直到这项工作，PIK3CA 突变和扩增与胃癌的临床结果之间的关联，特别是后者，仍没有很好的研究。
使用直接测序和实时定量 PCR，我们检测了 PIK3CA 突变和扩增及其与胃癌患者临床病理特征和临床结果的关联。
在 113 例胃癌患者中发现 PIK3CA 突变和扩增分别为 8/113（7.1%）和 88/131（67%）。PIK3CA 扩增与磷酸化 Akt（p-Akt）水平的升高密切相关。PIK3CA 突变与胃癌的临床病理特征和临床结果之间没有关系。PIK3CA 扩增与癌症相关的死亡显著正相关。重要的是，Kaplan-Meier 生存曲线显示，PIK3CA 扩增的患者生存时间明显短于没有 PIK3CA 扩增的患者。
我们的数据表明，PIK3CA 突变并不常见，但在胃癌中其扩增非常常见，可能是激活胃癌中 PI3K/Akt 途径的主要机制。重要的是，Kaplan-Meier 生存曲线显示，PIK3CA 扩增与胃癌患者的不良生存显著正相关。总的来说，PI3K/Akt 信号通路可能是胃癌的一个有效的治疗靶点。
