Establishment of CYFRA 21-1reference intervals for healthy Chinese adults from Nanning region of Guangxi province

Abstract Objective: To investigate the levels of serum CYFRA 21-1 of healthy adults in Nanning district of Guangxi, and establish reference intervals (RIs) of serum CYFRA 21-1 for healthy population in this area so as to provide more accurate basis for clinical screening, diagnosis and treatment of non-small cell lung cancer (NSCLC). Methods: Healthy subjects from Nanning district who went to International Zhuang Medicine Hospital Affiliated to Guangxi University of traditional Chinese medicine for physical examination were enrolled in this study. The level of serum CYFRA 21-1 was detected by Chemiluminescence microparticle immunoassay (CMIA). The RIs of CYFRA 21-1were established by nonparametric method according to the requirements of American Clinical & Laboratory Standards Institute (CLSI) EP28-A3c guideline. The established RIs were verified using healthy individuals from the same district who went to the hospital for physical examination between January 2022 and April 2022. Results: A total of 7352 cases who met the inclusion criteria were included in the study after the outliers were eliminated by Dixon method. The Kolmogorov-Smirnov Normality test showed a non-Gaussiandistribution of CYFRA 21-1. The Mann-Whitney U test showed that the serum CYFRA 21-1 levels were significantly different between males and females (p<0.01). The Spearman correlation analysis showed that serum CYFRA 21-1 levels were positively correlated with age (total: r=0.251, P=0.000; male: r=0.246, P=0.000; female: r=0.150, P=0.000). Therefore, the results of serum CYFRA 21-1 levels of males and females were divided into six groups according to age (≤30，31-40，41-50，51-60，61-70, and ≥71). The Kruskal-Wallis test showed that the results of serum CYFRA 21-1 levels of the males and females were both significant different among the six age groups (Male: H=275.707, p<0.01; Female H=121.911, p<0.01).Then the Mann-Whitney U test was used to compare the differences between the adjacent age groups in males and females. The results showed that there were statistical significant differences in 41-50 vs.31-40 (Z=-6.912, P=0.000), 51-60 vs.41-50 (Z=-7.959, P=0.000), ≥71 vs.61-70 (Z=-2.739, P=0.006) in males, and 31-40 vs.≤30 (Z=-2.665, P=0.008), 51-60 vs.41-50 (Z=-6.673, P=0.000), 61-70vs.51-60 (Z=-3.166, P=0.002) in females. Therefore, the ≤30 age group was combined with 31-40 age group, and the 51-60 age group was combined with 61-70 age group in males when established RIs, and the 31-40 age group was combined with 41-50 age group, the 61-70 age group was combined with ≥71 age group when established RIs in females. The established RIs were verified using the data of 573 healthy subjects and the results showed that more than 90% of the values of each group fell within the RIs of the each age group, indicating that the RIs established in this study was reliable and suitable for healthy population in this area. Conclusions: The age-stratified and gender­specific RIs for CYFRA21-1 in Nanning region of Guangxi province have been successfully established, which might contribute to better screening, diagnosis and treatment of NSCLC in this area.