Abstract:

Objective To prelimiarily establish the reference range of cytokeratin 19 （CYFRA21-1） by electro-chemiluminescence method and verify its applicability and the correlation with other relevant determination indicators. Methods A total of 1 642 apparently healthy subjects from Shanghai Municipal Hospital of Traditional Chinese Medicine of Shanghai University of Traditional Chinese Medicine from February 2023 to May 2024 were enrolled，and they were classified according to gender and age （≤40 years old，41-60 years old，≥61 years old）. Another 120 apparently healthy subjects who underwent routine physical examinations at the Shanghai Municipal Hospital of Traditional Chinese Medicine of Shanghai University of Traditional Chinese Medicine in May 2025 were enrolled for validating the self-established reference range. The serum CYFRA21-1 levels were determined by electro-chemiluminescence method，and the general data（gender，age）and laboratory indicator [carcinoembryonic antigen（CEA），alpha-fetoprotein（AFP），alanine aminotransferase（ALT），serum creatinine（SCr），fasting plasma glucose（FPG），total cholesterol（TC），triglyceride（TG）and white blood cell（WBC） count] results were collected. Spearman correlation analysis and partial correlation analysis were used to evaluate the correlation between CYFRA21-1 and other indicators. The reference range establishment procedure followed the requirements of the Clinical and Laboratory Standards Institute（CLSI）EP28-A3c document. Results Except for the difference in serum CYFRA21-1 levels between females in the ≤40-year-old group and those in the 41-60-year-old group（P>0.05），there was statistical significance in serum CYFRA21-1 levels among the other age groups of the same gender（P<0.001）. The serum CYFRA21-1 level of males in the 41-60-year-old group was higher than that of females（P=0.005），and there was no statistical significance between males and females in the ≤40-year-old group and ≥61-year-old group（P>0.05）. The upper limit of the reference range was set at the 95th percentile，and the reference range of CYFRA21-1 was established by age group：≤40 years old ≤3.47 ng·mL^-1，41-60 years old ≤4.08 ng·mL^-1，≥61 years old≤4.97 ng·mL^-1. After adjusting for age，CYFRA21-1 was positively correlated with CEA，SCr，FPG and WBC count （r values were 0.114，0.198，0.160 and 0.088，respectively，P<0.001）.Among the 120 apparently healthy subjects used for validating the reference range，the number of cases exceeding the reference range for those≤40 years old，40-60 years old and≥61 years old were 1（2.5%），1（2.5%）and 2（5.0%），respectively. The self-established reference range validation was successful. Conclusions The serum CYFRA21-1 level shows an increasing trend with age，and the reference range of CYFRA21-1 for different age groups in Shanghai has been preliminarily established.

Key words: Cytokeratin 19 fragment, Tumor marker, Reference range