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.
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 adenocarcinomapatients. 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.
Authors: Ayumu Taguchi; Allen D Taylor; Jaime Rodriguez; Müge Celiktaş; Hui Liu; Xiaotu Ma; Qing Zhang; Chee-Hong Wong; Alice Chin; Luc Girard; Carmen Behrens; Wan L Lam; Stephen Lam; John D Minna; Ignacio I Wistuba; Adi F Gazdar; Samir M Hanash Journal: Cancer Res Date: 2014-06-26 Impact factor: 12.701