title: Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer.
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.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, the People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Demao
authors.initials: D
authors.lastname: Yao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Hongjun
authors.initials: H
authors.lastname: Lv
authors.forename: Guanjun
authors.initials: G
authors.lastname: Zhang
authors.forename: Meiju
authors.initials: M
authors.lastname: Ji
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Nongyue
authors.initials: N
authors.lastname: He
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
mesh_terms: D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D053208:Kaplan-Meier Estimate; D009154:Mutation; D059645:Mutation Rate; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt