SCCA and CYFRA 21-1 Reference Intervals for Apparently Healthy Chinese Adults: a Multicenter Cross-Sectional Study.

Background: This study aimed to establish reference intervals for two biomarkers actively utilized in routine annual medical check-ups in China: squamous cell carcinoma antigen (SCCA) and cytokeratin 19 fragment (CYRFA 21-1), and to understand the influence of age, gender, and benign nodule(s) on their levels.

Methods: This prospective multicenter cross-sectional study continuously enrolled apparently healthy adults attending annual medical check-ups at three sites in 2019. Serum SCCA and CYFRA 21-1 levels were measured using electrochemiluminescence immunoassays. Age- and gender-specific reference intervals for the two biomarkers were established by using the 0 - 95th percentiles with 90% confidence intervals (CIs). The 97.5th percentiles were also provided.

Results: A total of 1,017 subjects were enrolled in this study. Both biomarkers were significantly lower in females, and age was negatively associated with SCCA while positively associated with CYFRA 21-1 (all p < 0.0001). No statistically significant differences were determined between subgroups without/with benign nodule(s) despite nodule(s) status (all p > 0.05). The overall reference interval for SCCA is 0 - 2.64 ng/mL and 0 - 4.39 ng/mL for CYFRA 21-1. The age-specific reference intervals for SCCA are 0 - 2.76 ng/mL (18 - 49 years) and 0 - 2.22 ng/mL (≥ 50 years), and for CYFRA 21-1, they are 0 - 3.86 ng/mL (18 - 49 years) and 0 - 4.89 ng/mL (≥ 50 years). The gender-specific reference intervals for SCCA are 0 - 2.83 ng/mL (male) and 0 - 2.49 ng/mL (female), and for CYFRA 21-1, they are 0 - 4.34 ng/mL (male) and 0 - 4.45 ng/mL (female).

Conclusions: The reference intervals for SCCA and CYFRA 21-1 established in this study could be utilized in annual medical check-ups and contribute to the screening of lung cancer in China.