OBJECTIVE: The main aims of this study were to explore the relationships between 
serum tumor markers and connective tissue disease-related interstitial lung 
disease (CTD-ILD) and to evaluate the clinical value of tumor markers for 
investigating interstitial lung disease (ILD) in patients with connective tissue 
disease (CTD).
METHODS: The study included 235 patients with CTD (90 CTD without ILDs, 145 
CTD-ILD). Clinical information and the levels of inflammatory and tumor markers, 
including carbohydrate antigen (CA) 19-9, CA125, carcinoembryonic antigen (CEA), 
CA153, and cytokeratin 19 fragments (CYFRA21-1), were obtained in all the 
patients.
RESULTS: A significant difference between CTD with or without ILD and higher 
levels of tumor markers was observed in the CTD-ILD group, including CA19-9 
(p<0.001), CEA (p<0.001), CA153 (p<0.001), and CYFRA21-1 (p<0.001). There was no 
significant difference in serum tumor marker levels in the various types of CTD 
(rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, 
inflammatory myositis, systemic sclerosis, and mixed connective tissue disease). 
The levels of CA153 [odds ratio (OR)=1.159] and CYFRA21-1 (OR=2.269) were 
clearly related to the risk of CTD-ILD. The diagnostic value of CA153 [area 
under receiver operating characteristic curve (AUC)=0.736] and CYFRA21-1 
(AUC=0.718) was confirmed for ILDs in CTD patients, at cut-off values of 9.45 
U/mL and 2.13 ng/mL, respectively.
CONCLUSION: There is a positive correlation between serum tumor marker levels 
and CTD-ILD. Higher levels of CA153 and CYFRA21-1 suggest an increased risk of 
developing ILD and may therefore be useful as biomarkers for detecting CTD-ILD 
in the clinical setting.