title: XAGE-1a and XAGE-1d are potential biomarkers of lung squamous cell carcinoma.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer deaths worldwide. We evaluated the diagnostic potential of sera XAGE-1a and XAGE-1d in lung cancer, both of which are variants of the X antigen family, member 1.
  
  
  METHODS
  The expression levels of XAGE-1a and XAGE-1d in cell lines were determined using western blot analysis. Competitive ELISA was used to analyze XAGE-1a and XAGE-1d levels in culture supernatants and sera from 194 lung cancer patients and 194 healthy sex- and age-group-matched controls. To evaluate the diagnostic performance of these proteins, we also analyzed carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) in culture supernatants and 388 sera using commercial ELISA kits.
  
  
  RESULTS
  XAGE-1a and XAGE-1d proteins were expressed in both breast cancer and lung cancer cell lines, but they were only secreted by the latter. The areas under the curves (AUCs) for XAGE-1a and XAGE-1d were 0.787 and 0.806, respectively. The cutoff values (sensitivity, specificity) for XAGE-1a and XAGE-1d were 1.62 ng/ml (0.866, 0.572) and 2.51 ng/ml (0.871, 0.613), respectively. The diagnostic performance was improved for patients with squamous cell carcinoma. The AUC values for XAGE-1a and XAGE-1d for patients with squamous cell carcinoma versus a group containing all healthy participants and patients with any illness other than squamous cell carcinoma were similar to those for CEA and CYFRA 21-1. Better performance (AUC: 0.914) for all patients was obtained when using a combination of four markers (Random Forest).
  
  
  CONCLUSIONS
  Sera XAGE-1a and XAGE-1d are potential biomarkers for lung cancer; they display a diagnostic performance comparable to that of CEA or CYFRA 21-1. Further studies are needed to evaluate the diagnostic and prognostic potential of XAGE-1a and XAGE-1d in lung cancer.
authors.affiliation: Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Ha
authors.forename: Hye Yeong
authors.initials: HY
authors.lastname: Sung
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Heon M
authors.initials: HM
authors.lastname: Lim
authors.forename: Hark Kyun
authors.initials: HK
authors.lastname: Kim
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D019540:Area Under Curve; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; C413656:XAGE1A protein, human; C102012:antigen CYFRA21.1