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

Abstract

BackgroundThe 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.MethodsUsing 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.ResultsPIK3CA 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.ConclusionsOur 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.

In vivo multiplexed interrogation of amplified genes identifies GAB2 as an ovarian cancer oncogene

“…We identified PI3K pathway alterations in 54% of the high-grade serous ovarian cancer samples we analyzed from the TCGA dataset. PIK3CA amplification was a common event and has been seen in other cancers (34,35). Co-occurrence of GAB2 amplification and PI3K pathway component alteration was observed in a subset of ovarian cancer samples.…”

138 Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer

“…PIK3CA mRNA and protein expression were reported to be significantly higher in gastric tumor tissues compared to normal gastric adjacent mucosa [12,21,22]. Furthermore, PIK3CA overexpression was described in other different tumor types [23,24].…”

The JAK/STAT signaling cascade in gastric carcinoma (Review)

“…PIK3CA is found to be mutated in 5% of gastric cancers in which mutation of this gene leads to the constitutive activation of the pathway even in the absence of ligand (29,49,50). Poor prognosis has also been associated with gastric cancer patients having amplified PIK3CA in advanced gastric cancer cases (51). Several clinical trials targeting molecules involved in this dysregulated signaling pathway are under investigation.…”