Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenocarcinoma / genetics*
-
Adenocarcinoma / metabolism
-
Adult
-
Aged
-
Biomarkers, Tumor / genetics*
-
Chromogranin A / biosynthesis
-
Chromogranin A / genetics
-
DNA Methylation / genetics*
-
Down-Regulation
-
Gene Expression Profiling
-
Glutathione Peroxidase / biosynthesis
-
Glutathione Peroxidase / genetics*
-
HSP47 Heat-Shock Proteins / biosynthesis
-
HSP47 Heat-Shock Proteins / genetics
-
Humans
-
Immunohistochemistry
-
Inhibin-beta Subunits / biosynthesis
-
Inhibin-beta Subunits / genetics
-
Kaplan-Meier Estimate
-
Kruppel-Like Factor 4
-
Kruppel-Like Transcription Factors / biosynthesis
-
Kruppel-Like Transcription Factors / genetics
-
Lipase / biosynthesis
-
Lipase / genetics
-
Middle Aged
-
Neoplasm Staging
-
Oligonucleotide Array Sequence Analysis
-
Promoter Regions, Genetic
-
Reverse Transcriptase Polymerase Chain Reaction
-
Somatostatin / biosynthesis
-
Somatostatin / genetics
-
Stomach Neoplasms / genetics*
-
Stomach Neoplasms / metabolism
-
Thy-1 Antigens / biosynthesis
-
Thy-1 Antigens / genetics
-
Tissue Array Analysis
-
Up-Regulation
Substances
-
Biomarkers, Tumor
-
Chromogranin A
-
HSP47 Heat-Shock Proteins
-
KLF4 protein, human
-
Kruppel-Like Factor 4
-
Kruppel-Like Transcription Factors
-
SERPINH1 protein, human
-
Thy-1 Antigens
-
inhibin beta A subunit
-
Somatostatin
-
Inhibin-beta Subunits
-
GPX3 protein, human
-
Glutathione Peroxidase
-
Lipase
-
gastric lipase, human