title: Concomitant PIK3CA amplification and RASSF1A or PAX6 hypermethylation predict worse survival in gastric cancer.
abstract: OBJECTIVE
  A large number of genetic and epigenetic alterations have been found in gastric cancer, but there is remarkably little consensus on the value of individual biomarker in diagnosis and prognosis of this cancer. This study was designed to illustrate the value of PIK3CA amplification in combination with promoter methylation of RASSF1A and PAX6 genes in early diagnosis and prognosis of gastric cancer.
  
  
  METHODS
  Using real-time quantitative PCR, quantitative methylation-specific PCR (Q-MSP), and methylation-specific PCR (MSP) assays, we examined PIK3CA amplification and promoter methylation of RASSF1A and PAX6 genes in a cohort of gastric cancers, and explored the association of various (epi)genotypes with clinical outcomes of gastric cancer patients.
  
  
  RESULTS
  We demonstrated that PIK3CA gene was specifically amplified in gastric cancers, but not in normal gastric tissues. Moreover, frequent methylation of RASSF1A and PAX6 was also found in gastric cancers. Given the patients harboring diverse (epi)genotypes, we thus investigated the effect of various (epi)genotypes on poor prognosis in gastric cancer. The data showed that concomitant PIK3CA amplification and RASSF1A or PAX6 methylation were closely associated with poor clinical outcomes, particularly survival, as compared to other (epi)genotypes in gastric cancer.
  
  
  CONCLUSIONS
  We found frequent PIK3CA amplification and promoter methylation of RASSF1A and PAX6 genes in gastric cancers, and demonstrated that concomitant PIK3CA amplification and promoter methylation in any one of these two genes were significantly associated with worse survival in gastric cancer. Collectively, such (epi)genotypes may be strong and independent poor prognostic factors for gastric cancer patients.
authors: Qi
authors: Q
authors: Yang
authors: Yuan
authors: Y
authors: Shao
authors: Jing
authors: J
authors: Shi
authors: Yiping
authors: Y
authors: Qu
authors: Kexia
authors: K
authors: Wu
authors: Siwen
authors: S
authors: Dang
authors: Bingyin
authors: B
authors: Shi
authors: Peng
authors: P
authors: Hou
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D058534:Class I Phosphatidylinositol 3-Kinases; D019175:DNA Methylation; D017931:DNA Primers; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C411762:RASSF1 protein, human; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human