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XAGE-1 Expression in Non–Small Cell Lung Cancer and Antibody Response in Patients

Authors' Affiliations: Departments of ¹ Immunology, ² Oncology and Thoracic Surgery and ³ Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan and ⁴ Department of Surgery, Division of Gastroenterology, Kawasaki Medical School, Kurashiki, Japan

Requests for reprints: Eiichi Nakayama, Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan. Phone: 81-86-235-7187; Fax: 81-86-235-7193; E-mail: nakayama{at}md.okayama-u.ac.jp.

Purpose: XAGE-1 was originally identified by the search for PAGE/GAGE-related genes using expressed sequence tag database and was shown to exhibit characteristics of cancer/testis-like antigens. Four transcript variants XAGE-1a, XAGE-1b, XAGE-1c, and XAGE-1d have been identified thus far. We recently identified XAGE-1b as a dominant antigen recognized by sera from lung adenocarcinoma patients. We here investigated the mRNA expression of four XAGE-1 variants and XAGE-1 protein expression in non–small cell lung cancer (NSCLC). Humoral immune response to XAGE-1b was also evaluated in patients.

Experimental Design: Forty-nine NSCLC specimens were analyzed for the expression of four XAGE-1 transcript variants by conventional 30-cycle and real-time reverse transcription-PCR and XAGE-1 protein expression by immunohistochemistry. Sera from 74 patients were analyzed for XAGE-1b antibody production by ELISA and Western blot.

Results: XAGE-1b and XAGE-1d mRNA were detected in 15 and 6 of 49 lung cancer specimens, respectively. No XAGE-1a or XAGE-1c mRNA expression was observed. XAGE-1b mRNA expression was observed in 14 of 31 (45%) adenocarcinoma and 1 of 18 (6%) lung cancer with other histologic types. Immunohistochemical analysis using a XAGE-1 monoclonal antibody showed that 14 of 15 XAGE-1b mRNA-positive and 3 of 34 XAGE-1b mRNA-negative specimens expressed XAGE-1 protein. Seropositivity was observed in 5 of 56 patients with adenocarcinoma, whereas none of 18 patients with other histologic types produced XAGE-1b antibody.

Conclusion: XAGE-1b is highly and strongly expressed in lung adenocarcinoma and immunogenic in patients, suggesting that XAGE-1b is a promising antigen for immunotherapy against lung adenocarcinoma.

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