RRC ID 43742
著者 Kobayashi M, Matsumoto T, Ryuge S, Yanagita K, Nagashio R, Kawakami Y, Goshima N, Jiang SX, Saegusa M, Iyoda A, Satoh Y, Masuda N, Sato Y.
タイトル CAXII Is a sero-diagnostic marker for lung cancer.
ジャーナル PLoS One
Abstract To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using pulmonary adenocarcinoma (AD)-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, we selected an antibody designated as KU-Lu-5 which showed intense membrane staining of A549 cells. Based on immunoprecipitation and MADLI TOF/TOF-MS analysis, this antibody was recognized as carbonic anhydrase XII (CAXII). To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed dot blot analysis with a training set consisting of sera from 70 lung cancer patients and 30 healthy controls. The CAXII expression levels were significantly higher in lung cancer patients than in healthy controls in the training set (P<0.0001), and the area under the curve of ROC was 0.794, with 70.0% specificity and 82.9% sensitivity. In lung cancers, expression levels of CAXII were significantly higher in patients with squamous cell carcinoma (SCC) than with AD (P = 0.035). Furthermore, CAXII was significantly higher in well- and moderately differentiated SCCs than in poorly differentiated ones (P = 0.027). To further confirm the utility of serum CAXII levels as a sero-diagnostic marker, an additional set consisting of sera from 26 lung cancer patients and 30 healthy controls was also investigated by dot blot analysis as a validation study. Serum CAXII levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P = 0.030). Thus, the serum CAXII levels should be applicable markers discriminating lung cancer patients from healthy controls. To our knowledge, this is the first report providing evidence that CAXII may be a novel sero-diagnostic marker for lung cancer.
巻・号 7(3)
ページ e33952
公開日 2012-1-1
DOI 10.1371/journal.pone.0033952
PII PONE-D-11-18726
PMID 22439015
PMC PMC3306309
MeSH Adenocarcinoma / diagnosis Adenocarcinoma / enzymology Aged Antibodies, Monoclonal, Murine-Derived Antibody Specificity Biomarkers, Tumor / blood* Biomarkers, Tumor / immunology Biomarkers, Tumor / metabolism Carbonic Anhydrases / blood* Carbonic Anhydrases / immunology Carbonic Anhydrases / metabolism Carcinoma, Large Cell / diagnosis Carcinoma, Large Cell / enzymology Carcinoma, Neuroendocrine / diagnosis Carcinoma, Neuroendocrine / enzymology Carcinoma, Small Cell / diagnosis Carcinoma, Small Cell / enzymology Carcinoma, Squamous Cell / diagnosis Carcinoma, Squamous Cell / enzymology Case-Control Studies Cell Line, Tumor Female Humans Immunohistochemistry Lung Neoplasms / diagnosis* Lung Neoplasms / enzymology* Male Serologic Tests
IF 2.74
引用数 21
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 LC-2/ad(RCB0440) RERF-LC-AI(RCB0444) SP2/0-Ag14(RCB0209)