Mutations in PI3K/AKT pathway genes and amplifications of PIK3CA are associated with patterns of recurrence in gastric cancers

Wen Liang Fang, Kuo Hung Huang, Yuan Tzu Lan, Chien Hsing Lin, Shih Ching Chang*, Ming Huang Chen, Yee Chao, Wen Chang Lin, Su Shun Lo, Anna Fen Yau Li, Chew Wun Wu, Shih Hwa Chiou, Yi Ming Shyr

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Mutations in genes involved in the PI3K/AKT pathway and amplifications of the PIK3CA gene in gastric cancer and their associations with clinicopathological characteristics and EBV infection were analyzed in this study. A total of 431 patients with gastric adenocarcinomas were enrolled, and 39 mutation hotspots were evaluated in these patients using MALDI-TOF mass spectrometry were analyzed. PIK3CA amplifications were analyzed using real-time quantitative PCR. Regarding patients with intestinal-type gastric cancer, those with mutations in PI3K/AKT pathway genes were also more likely to have tumors located in the lower-third of the stomach than were those without mutations. Regarding patients with diffuse-type gastric cancer, those with PI3K/AKT pathway mutations were more likely to have tumors located in the upper-third of the stomach and to have more hematogenous metastases, particularly in the liver and lungs, than were patients without such mutations (22.2% vs. 4.5%). No significant survival difference was observed between patients with vs. without PI3K/AKT pathway mutations. Mutations in PI3K/ AKT pathway genes were associated with hematogenous metastasis in patients with diffuse-type gastric cancer. Only when the tumors were located in the middle-third of stomach, tumor with mutations of the PIK3CA gene or mutations of the PI3K/ AKT pathway genes were associated with more EBV infection than those without mutations. Patients with PIK3CA amplifications were more likely to have diffusetype and poorly differentiated gastric cancers and were more likely to experience peritoneal recurrence compared with those without PIK3CA amplifications. Even upon subgroup analysis, PI3KCA amplifications were found to not affect the patients' outcomes.

Original languageEnglish
Pages (from-to)6201-6220
Number of pages20
JournalOncotarget
Volume7
Issue number5
DOIs
StatePublished - 2016

Keywords

  • Diffuse-type
  • PI3K/AKT pathway
  • PIK3CA amplifications
  • Prognosis
  • Recurrence pattern

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