title: Prognostic significance of glutathione peroxidase 1 (GPX1) down-regulation and correlation with aberrant promoter methylation in human gastric cancer.
abstract: BACKGROUND
  This study aimed at examining the association of gene silencing and promoter methylation of glutathione peroxidase 1 (GPX1) and glutathione peroxidase 3 (GPX3) in gastric cancer cells and determined the clinical significance of GPX1 and GPX3 expression loss in gastric cancer tissue.
  
  
  METHODS
  Analysis of mRNA expression was carried out by reverse transcription-polymerase chain reaction (RT-PCR). Methylation of the GPX1 promoter region was analyzed by bisulfite sequencing, and that of the GPX3 promoter region was analyzed by methylation-specific PCR (MSP). Tissue microarray-based immunohistochemistry of GPX1 and GPX3 in 1,163 resected gastric cancer specimens was performed to assess the associations with clinicopathological parameters.
  
  
  RESULTS
  Reduced GPX1 and GPX3 mRNA expression was associated with promoter methylation in gastric cancer cell lines. A correlation between DNA promoter methylation and loss of GPX1 expression was noted in 16 gastric cancer tissue samples (p=0.005). Loss of GPX1 and GPX3 proteins was found in 24.4% and 30.8% of gastric cancer tissues. Loss of GPX1 expression was significantly associated with advanced gastric cancer (p=0.039) and lymphatic invasion (p=0.010); loss of GPX3 expression was associated with advanced gastric cancer (p<0.001) and lymph node metastasis (p<0.001). Kaplan-Meier analysis showed that low expression of GPX1 was associated with poor cancer-specific survival (p=0.010).
  
  
  CONCLUSIONS
  Data from this study implicate aberrant hypermethylation of promoter regions of GPX1 and GPX3 as a mechanism for down-regulation of GPX1 and GPX3 mRNA expression in gastric cancer cells. Loss of GPX1 expression was associated with aggressiveness and poor survival in patients with gastric cancer.
authors: Department of Pathology, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Republic of Korea.
authors: Sun Young
authors: SY
authors: Min
authors: Hee Sung
authors: HS
authors: Kim
authors: Eun Jung
authors: EJ
authors: Jung
authors: Eun Ji
authors: EJ
authors: Jung
authors: Chang Do
authors: CD
authors: Jee
authors: Woo Ho
authors: WH
authors: Kim
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D017931:DNA Primers; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human