Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer
- 5 December 2005
- journal article
- oncogenomics
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 25 (17), 2546-2557
- https://doi.org/10.1038/sj.onc.1209279
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue will be useful molecular markers for diagnosis and may also be good therapeutic targets. However, little is known about cancer-specific genes, at least in GC. In this study, we searched for GC-specific genes by serial analysis of gene expression (SAGE) data analysis and quantitative reverse transcription (RT)–PCR. Comparing GC SAGE libraries with those of various normal tissues in the SAGEmap database, we identified 54 candidate GC-specific genes. Quantitative RT–PCR analysis of these candidates revealed that APin protein (APIN), taxol resistance-associated gene 3 (TRAG3), cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1), melanoma inhibitory activity (MIA), matrix metalloproteinase-10 (MMP-10), dickkopf homolog 4 (DKK4), GW112, regenerating islet-derived family, member 4 (REGIV), and HORMA domain-containing 1 (HORMAD1) were expressed much more highly in GC than in 14 kinds of normal tissues. Immunohistochemical staining for MIA, MMP-10, and DKK4 was found in 47 (31.1%), 68 (45.0%), and two (1.3%) of 151 GCs, respectively, and staining for both MIA and MMP-10 was correlated with poor prognosis in advanced GC (P=0.0001 and 0.0141, respectively). Moreover, enzyme-linked immunosorbent assay showed high levels of MMP-10 (65/69, 94.2%) in serum samples from patients with GC. Levels of MIA were raised in a small proportion of serum samples from patients with GC (4/69, 5.8%). In Boyden chamber invasion assays, MIA-transfected GC cells were up to three times more invasive than cells transfected with empty vector. Taken together, these results suggest that MMP-10 is a good marker for the detection of GC and that MIA and MMP-10 are prognostic factors for GC. As expression of MIA and MMP-10 is narrowly restricted in cancer, these two molecules may be good therapeutic targets for GC.Keywords
This publication has 40 references indexed in Scilit:
- Melanoma Inhibitory Activity (MIA) increases the invasiveness of pancreatic cancer cellsCancer Cell International, 2005
- Tissue repair and stem cell renewal in carcinogenesisNature, 2004
- Tissue-Wide Expression Profiling Using cDNA Subtraction and Microarrays to Identify Tumor-Specific GenesCancer Research, 2004
- Gastic cancerThe Lancet, 2003
- The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics AssessmentGenome Research, 2003
- Overexpression of Matrix Metalloproteinase-10 and Matrix Metalloproteinase-3 in Human Diabetic Corneas: A Possible Mechanism of Basement Membrane and Integrin AlterationsThe American Journal of Pathology, 2001
- Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinomaThe American Journal of Surgery, 1999
- In situ expression patterns of melanoma-inhibiting activity (MIA) in melanomas and breast cancersThe Journal of Pathology, 1999
- Cloning of a Retinoic Acid-sensitive mRNA Expressed in Cartilage and during ChondrogenesisPublished by Elsevier BV ,1996
- Immunolocalisation studies on six matrix metalloproteinases and their inhibitors, TIMP-1 and TIMP-2, in synovia from patients with osteo- and rheumatoid arthritis.Annals Of The Rheumatic Diseases, 1995