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Open Access Research article

Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer

Jing Shi1, Demao Yao2, Wei Liu1, Na Wang1, Hongjun Lv1, Guanjun Zhang3, Meiju Ji1, Li Xu1, Nongyue He4, Bingyin Shi1 and Peng Hou1*

Author affiliations

1 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, the People's Republic of China

2 Department of Surgery, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, the People's Republic of China

3 Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, the People's Republic of China

4 State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, the People's Republic of China

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Citation and License

BMC Cancer 2012, 12:50  doi:10.1186/1471-2407-12-50

Published: 1 February 2012

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords:
Gastric cancer; PI3K/Akt pathway; PIK3CA mutations; PIK3CA amplification; Poor survival