title: XAGE-1 expression in non-small cell lung cancer and antibody response in patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Akiko
authors.initials: A
authors.lastname: Uenaka
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Sato
authors.forename: Hideo
authors.initials: H
authors.lastname: Okumura
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Michihide
authors.initials: M
authors.lastname: Shimono
authors.forename: Ali Mohamed
authors.initials: AM
authors.lastname: Ali Eldib
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ono
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ohara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yamashita
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Motoi
authors.initials: M
authors.lastname: Aoe
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D020224:Expressed Sequence Tags; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; C413656:XAGE1A protein, human