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Opa Interacting Protein 5 (OIP5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer
Authors:Yoshito Nakamura  Fumiaki Tanaka  Hisashi Nagahara  Keisuke Ieta  Naotsugu Haraguchi  Koshi Mimori  Atsushi Sasaki  Hiroshi Inoue  Katsuhiko Yanaga  Masaki Mori
Affiliation:(1) Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan;(2) Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama, Japan;(3) Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan
Abstract:Background Identification of novel cancer-specific antigens is important for the advancement of immunotherapy. Our aim was to identify cancer-specific genes in gastric cancer. Methods Using cDNA microarray analysis, we detected genes overexpressed specifically in gastric cancer cells. The expression levels of selected genes, including OIP5, was confirmed by real time RT-PCR analysis in tumor/normal paired bulk samples of 58 clinical cases. The expression levels of selected genes in normal tissues were also determined with a human total RNA master panel. We also compared the expression status of OIP5 with that of the other known cancer-testis specific genes. Results Twenty-two genes were determined to be upregulated in gastric cancer cells. Among these, three genes (CDC6, Exo1, and OIP5) were selected and confirmed to be upregulated in the tumor tissue compared to normal tissue. A human total RNA master panel demonstrated that OIP5, but not Exo1 or CDC6, showed high specificity in testis. Thus OIP5 may be considered a cancer-testis specific gene. In 58 clinical cases of gastric cancer examined, we found OIP5 gene expression in 27 cases (47%). Thirteen of these 27 cases showed no expression of the known cancer specific genes such as MAGE-1, MAGE-3 or NY-ESO-1. Conclusions Using a combination of LMD and microarray, we identified OIP5 as a cancer-testis specific gene. Further expression analysis in a set of clinical cases revealed that OIP5 may be a novel immunotherapy target for patients with gastric cancer. Grant sponsors: CREST, JST; Uehara Memorial Foundation; Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 17015032, 17109013, 17591411, 17591413, and 16390381; Health and Labour Sciences Research Grants; Third Term Comprehensive Control Research for Cancer, 16271201.
Keywords:OIP5    PRAME   Gastric cancer  Laser micro dissection  Cancer testis antigen
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