XAGE-1 expression in non-small cell lung cancer and antibody response in patients

Kazuhiko Nakagawa, Yuji Noguchi, Akiko Uenaka, Shuichiro Sato, Hideo Okumura, Motoyuki Tanaka, Michihide Shimono, Ali Mohamed Ali Eldib, Toshiro Ono, Nobuya Ohara, Tadashi Yoshino, Kazuki Yamashita, Tsukasa Tsunoda, Motoi Aoe, Nobuyoshi Shimizu, Eiichi Nakayama

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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, ana 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 m RNA 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 XX1Gf-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.

Original languageEnglish
Pages (from-to)5496-5503
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number15
DOIs
Publication statusPublished - Aug 1 2005

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nakagawa, K., Noguchi, Y., Uenaka, A., Sato, S., Okumura, H., Tanaka, M., Shimono, M., Eldib, A. M. A., Ono, T., Ohara, N., Yoshino, T., Yamashita, K., Tsunoda, T., Aoe, M., Shimizu, N., & Nakayama, E. (2005). XAGE-1 expression in non-small cell lung cancer and antibody response in patients. Clinical Cancer Research, 11(15), 5496-5503. https://doi.org/10.1158/1078-0432.CCR-05-0216