An 8-gene signature, including methylated and down-regulated glutathione peroxidase 3, of gastric cancer.
We have identified an 8-gene signature with significant expression differences between gastric cancer and normal gastric tissues. This 8-gene set can predict the normal and cancer status of gastric tissues with more than 96% accuracy in a totally independent microarray dataset. The 8 genes are composed of down-regulated KLF4, GPX3, SST and LIPF, together with up-regulated SERPINH1, THY1 and INHBA in gastric cancer. To corroborate the differential gene expression pattern, we chose GPX3 and examined its expression pattern in detail. A comparison of GPX3 expression pattern shows a broader down-regulated pattern in multiple types of cancers, including cervical, thyroid, head and neck, lung cancers and melanoma than in healthy controls. An immuno-histostaining analysis in tissue microarrays confirms GPX3 down-regulation in gastric cancer. Mechanism-wise GPX3 down-regulation in gastric cancer is due to promoter hypermethylation. Collectively, these results show a correct identification of 8 genes as gastric cancer biomarkers.
Zhang
Xianglan
X
Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul 120-752, Korea.
Yang
Jung-Jin
JJ
Kim
Yoon Sun
YS
Kim
Ki-Yeol
KY
Ahn
Woong Shick
WS
Yang
Sanghwa
S
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D053379:Chromogranin A / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D050958:HSP47 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D028322:Inhibin-beta Subunits / Q000096:biosynthesis / Q000235:genetics; D053208:Kaplan-Meier Estimate; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D008049:Lipase / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000096:biosynthesis / Q000235:genetics; D046888:Tissue Array Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D005979:Glutathione Peroxidase; D050958:HSP47 Heat-Shock Proteins; D028322:Inhibin-beta Subunits; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008049:Lipase; D013004:Somatostatin; D018800:Thy-1 Antigens; C000715467:KLF4 protein, human; C494660:SERPINH1 protein, human; C103008:inhibin beta A subunit; C486484:GPX3 protein, human; C485982:LIPF protein, human