Assessment of tumor biomarkers for prognosis in interstitial lung disease associated with connective tissue disease: a prospective study.

Background: There is uncertainty with respect to the baseline tumor markers and clinical outcomes for patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The study aimed to assess the association between baseline tumor markers and progressive pulmonary fibrosis (PPF) and prognosis. Methods: This is a prospective cohort study. Serum levels of nine tumor markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE), squamous cell carcinoma (SCC) antigen, cytokeratin fraction 21-1 (CYFRA21-1), serum ferritin (SF), alpha-fetoprotein (AFP) and carbohydrate antigen 724 (CA724) were collected at baseline in patients with CTD-ILD and healthy controls (HCs). Logistic regression and receiver operating characteristic (ROC) curves were used to assess the strength of baseline tumor markers in identifying PPF in CTD-ILD. Correlation analysis was performed to explore associations between tumor markers and disease severity. The relationship of prognosis and these markers was also evaluated. Results: There were 224 patients with CTD-ILD and 63 HCs included in the analysis. The serum CEA and CA125 levels were significantly higher in the PPF group than in the non-PPF and HC groups. The area under the ROC curve (AUC) of CEA was 0.64 [95% confidence interval (CI): 0.56-0.72], the highest among the tested tumor markers. For CA125, the AUC was 0.59 (95% CI: 0.51-0.68). Patients were then stratified into low-titre and high-titre groups based on the median levels of CEA or CA125. Compared with the low CEA group, patients in the high CEA group showed a higher risk for PPF [odds ratio (OR): 3.42, 95% CI: 1.74-6.72, P<0.001], while compared with the low CA125 group, patients in the high CA125 group had an OR of 1.96 (95% CI: 1.08-3.55, P=0.03). Elevated CEA concentration remained a significant risk factor of PPF in multivariate analysis, but CA125 did not. Furthermore, elevated CEA levels was also an independent risk factor associated with all-cause mortality and acute exacerbation (AE) in CTD-ILD patients. Conclusions: Circulating CEA may be associated with pulmonary fibrosis progression and prognosis of CTD-ILD.