Calnexin is a novel sero-diagnostic marker for lung cancer.
To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using lung adenocarcinoma (AC)-derived A549 cells as antigens by employing the random immunization method. Hybridoma supernatants were immunohistochemically screened for antibodies with AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice through limiting dilutions. From the obtained monoclonal antibodies, one designated as KU-Lad-001 was recognized as calnexin (CANX) based on immunoprecipitation and MADLI TOF/TOF-MS analysis. To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed reverse-phase protein array analysis with samples of 195 lung cancer patients and 100 healthy controls. The CANX expression levels were significantly higher in lung cancer patients than in healthy controls (P<0.0001), and the area under the curve of ROC was 0.980, with 96.9% specificity and 99.0% sensitivity. Furthermore, since CANX was also detected in stage I disease, the serum CANX levels should be applicable markers discriminating lung cancer patients from healthy controls and possibly used in the detection of early lung cancer. To our knowledge, the present results provide evidence that CANX may be a novel sero-diagnostic marker for lung cancer.
Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan; Research Fellow of the Japan Society for the Promotion of Science, Japan.
Makoto
M
Kobayashi
Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan; Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, Kanagawa, Japan.
Ryo
R
Nagashio
Department of Pathology, School of Medicine, Kitasato University, Kanagawa, Japan.
Shi-Xu
SX
Jiang
Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan.
Keita
K
Saito
Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan.
Benio
B
Tsuchiya
Department of Respiratory Medicine, School of Medicine, Kitasato University, Kanagawa, Japan.
Shinichiro
S
Ryuge
Department of Respiratory Medicine, School of Medicine, Kitasato University, Kanagawa, Japan.
Ken
K
Katono
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kitasato University, Kanagawa, Japan.
Hiroyasu
H
Nakashima
Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
Eriko
E
Fukuda
Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
Naoki
N
Goshima
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kitasato University, Kanagawa, Japan.
Yukitoshi
Y
Satoh
Department of Respiratory Medicine, School of Medicine, Kitasato University, Kanagawa, Japan.
Noriyuki
N
Masuda
Department of Pathology, School of Medicine, Kitasato University, Kanagawa, Japan.
Makoto
M
Saegusa
Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan; Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, Kanagawa, Japan. Electronic address: yuichi@med.kitasato-u.ac.jp.
Yuichi
Y
Sato
D000230:Adenocarcinoma / Q000175:diagnosis / Q000276:immunology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology*; D037281:Calnexin / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D040081:Protein Array Analysis / Q000379:methods
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037281:Calnexin
Antibody-based proteomics; Calnexin; Lung cancer; Sero-diagnostic marker