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Expression Profile of Cancer-Testis Genes in 121 Human Colorectal Cancer Tissue and Adjacent Normal Tissue

¹ Department of Colorectal Surgery and ² Cancer Biological Therapy and Diagnosis Center, Peking University School of Oncology, Beijing Cancer Hospital, Beijing, PR China; and ³ Oncology Research, Centocor, Inc., Malvern, Pennsylvania

Requests for reprints: Jin Gu and Yu Wang, Beijing Cancer Hospital, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, PR China. Phone: 86-10-88141032; Fax: 86-10-88122437/455; E-mail: zlguj{at}sun.bjmu.edu.cn.

Purpose: Among tumor antigens identified to date, cancer-testis (CT) antigens, which are coded by CT genes, are identified as a group of highly attractive targets for cancer vaccines. This study is the first to analyze the mRNA expression and possible correlation with pathologic characteristics of multiple CT genes in a large cohort of colorectal cancer (CRC) patients.

Experimental Design: The expression of 10 individual CT genes in 121 CRC and adjacent tissues were analyzed by RT-PCR method. The presence of autologous antibodies against NY-ESO-1 was examined in serum samples by ELISA. To confirm the protein expression, immunohistochemistry was done for detecting the NY-ESO-1 antigen in mRNA-positive CRC tissues.

Results: The CT genes were detected with various frequencies in CRC tissue, SCP-1, 1.7%; SSX-2, 2.5%; SSX-4, 2.5%; SSX-1, 5.0%; CT10, 6.6%; NY-ESO-1, 9.9%; MAGE-1, 11.6%; LAGE-1, 15.7%; MAGE-4, 22.3%; and MAGE-3, 27.3%. In 56.2% of tumor tissues examined in this study, at least one CT gene was detected. In contrast, no CT gene expression was found in cancer adjacent tissues. Among 10 CT genes investigated, NY-ESO-1 and LAGE-1 are of particular interest because their mRNA expression in CRC was rarely reported before. In our study, NY-ESO-1 mRNA was found to express in 9.9% of the samples, and also correlated significantly with stages (P = 0.041) and local lymph node metastasis (P = 0.002). In addition, we also identified one NY-ESO-1 antibody–positive serum sample. MAGE-4 mRNA was expressed at a high frequency in tumor tissues with vessel emboli samples (P = 0.025).

Conclusions: These results suggested that CT genes, especially NY-ESO-1 and LAGE-1, do express in CRC. More than 50% of the CRC patients in this study express at least one CT gene, making them eligible for CT vaccination. NY-ESO-1 gene may serve as a marker for local metastasis and advanced disease. MAGE-4 gene is significantly associated with the vessel emboli.

Key Words: Cancer-testis gene • colorectal carcinoma • immunotherapy

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