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10.1245/s10434-006-9121-x
Annals of Surgical Oncology 14:885-892 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Opa Interacting Protein 5 (OIP5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer

Yoshito Nakamura1,2,3, Fumiaki Tanaka1,2, Hisashi Nagahara1,2, Keisuke Ieta1,2, Naotsugu Haraguchi1,2, Koshi Mimori1,2, Atsushi Sasaki1,2, Hiroshi Inoue1,2, Katsuhiko Yanaga3 and Masaki Mori1,2

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

Correspondence: Address correspondence and reprint requests to: Masaki Mori; E-mail: mmori{at}beppu.kyushu-u.ac.jp

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 up-regulated 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.

Key Words: OIP5 • PRAME • Gastric cancer • Laser micro dissection • Cancer testis antigen

Abbreviations: OIP5, Opa interacting protein • 5CTA, cancer testis antigen • GAPDH, glyceraldehyde 3-phosphate dehydrogenase • LMD, laser microdissection • RT-PCR, reverse transcriptase-polymerase chain reaction






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