XAGE-1 expression in non-small cell lung cancer and antibody response in patients.
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.
Nakagawa
Kazuhiko
K
Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Noguchi
Yuji
Y
Uenaka
Akiko
A
Sato
Shuichiro
S
Okumura
Hideo
H
Tanaka
Motoyuki
M
Shimono
Michihide
M
Ali Eldib
Ali Mohamed
AM
Ono
Toshiro
T
Ohara
Nobuya
N
Yoshino
Tadashi
T
Yamashita
Kazuki
K
Tsunoda
Tsukasa
T
Aoe
Motoi
M
Shimizu
Nobuyoshi
N
Nakayama
Eiichi
E
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
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; C413656:XAGE1A protein, human