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.