Evaluation of squamous cell carcinoma antigen as a diagnostic biomarker in pulmonary diseases: a male cohort study

Early pulmonary disease recognition in men is often hindered by nonspecific clinical features and overlapping laboratory parameters. Squamous Cell Carcinoma Antigen (SCCA), a glycoprotein traditionally associated with malignancy, has been proposed as a potential biomarker in a wider spectrum of pulmonary disorders. This study evaluated the diagnostic performance of serum SCCA in pulmonary diseases among the male cohort and determined its relationship with inflammatory markers. We analyzed serum SCCA levels in 533 male patients diagnosed with squamous cell carcinoma (SCC), pneumonia, pulmonary nodules, or chronic obstructive pulmonary disease (COPD) at the Affiliated Hospital of Putian University (January 2017–November 2021), and compared them to 80 healthy male controls. Intergroup differences were assessed, correlations between SCCA and inflammatory markers were analyzed, and receiver operating characteristic (ROC) curves were used to determine disease-specific diagnostic performance. Serum SCCA levels differed significantly across disease groups. SCC patients had markedly higher concentrations (7.14 ± 3.64 ng/ml) than all other groups, whereas pulmonary nodules showed the lowest levels (1.45 ± 0.81 ng/ml). SCCA achieved its highest diagnostic accuracy in SCC (AUC = 0.792), outperforming its ability to differentiate other pulmonary conditions. Serum SCCA expression shows a promising and supportive biomarker in the diagnostic evaluation of pulmonary diseases among the male patients, meriting further validation in larger, multi-centre studies. Biomarker discovery remains central to improving diagnostic precision in pulmonary medicine. Although Squamous Cell Carcinoma Antigen (SCCA) has been widely investigated in oncological settings, its diagnostic relevance across malignant and non-malignant pulmonary diseases remains incompletely characterized. By systematically evaluating serum SCCA levels in patients with pulmonary squamous cell carcinoma, pneumonia, pulmonary nodules, and chronic obstructive pulmonary disease, and applying ROC-based diagnostic analysis, this study provides additional evidence supporting the potential utility of SCCA as an adjunctive biomarker for disease differentiation. The findings contribute to ongoing biomarker validation efforts and suggest that SCCA may have value when integrated with established clinical, radiological, and histopathological assessments to improve pulmonary disease characterization. Because the study was limited to a male cohort, further investigations including both sexes are needed to determine the broader clinical applicability of these findings.