Correlation Between Serum Tumor Marker Levels and Connective Tissue Disease-Related Interstitial Lung Disease

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.

[1]  Min Yang,et al.  Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population , 2021, Rheumatology and Therapy.

[2]  X. Gui,et al.  Cytokeratin 19 fragment is associated with severity and poor prognosis of interstitial lung disease in anti-MDA5 antibody-positive dermatomyositis. , 2021, Rheumatology.

[3]  Joyce S Lee,et al.  Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs) , 2020, Annals of the Rheumatic Diseases.

[4]  Xiaofeng Li,et al.  Increases in tumor markers are associated with primary Sjögren’s syndrome-associated interstitial lung disease , 2020, Therapeutic advances in chronic disease.

[5]  Y. Allanore,et al.  Circulating lung biomarkers in idiopathic lung fibrosis and interstitial lung diseases associated with connective tissue diseases: Where do we stand? , 2020, Seminars in arthritis and rheumatism.

[6]  E. Lee,et al.  Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease , 2019, Arthritis Research & Therapy.

[7]  Atit Silsirivanit Glycosylation markers in cancer. , 2019, Advances in clinical chemistry.

[8]  G. Sargin Tumor-Associated Antigens in Rheumatoid Arthritis Interstitial Lung Disease or Malignancy? , 2018, Archives of rheumatology.

[9]  P. Sarzi-Puttini,et al.  Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review , 2018, Expert review of clinical immunology.

[10]  M. Duffy,et al.  Tissue and Blood Biomarkers in Lung Cancer: A Review. , 2018, Advances in clinical chemistry.

[11]  T. Ueland,et al.  High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis. , 2016, Chest.

[12]  B. Liang,et al.  Tumour markers in rheumatoid arthritis-associated interstitial lung disease. , 2016, Clinical and experimental rheumatology.

[13]  S. Mathai,et al.  Management of interstitial lung disease associated with connective tissue disease , 2016, BMJ : British Medical Journal.

[14]  S. Wongkham,et al.  YKL-40/chitinase-3-like protein 1 is associated with poor prognosis and promotes cell growth and migration of cholangiocarcinoma , 2016, Tumor Biology.

[15]  M. Yildizgoren,et al.  Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study , 2016, Clinical Rheumatology.

[16]  G. Verleden,et al.  CYFRA 21.1 in bronchoalveolar lavage of idiopathic pulmonary fibrosis patients , 2015, Experimental lung research.

[17]  G. Washko,et al.  Detection of Rheumatoid Arthritis-Interstitial Lung Disease Is Enhanced by Serum Biomarkers. , 2015, American journal of respiratory and critical care medicine.

[18]  S. Kreiner,et al.  Serum YKL-40: a new independent prognostic marker for skeletal complications in patients with multiple myeloma , 2015, Leukemia & lymphoma.

[19]  P. Zanen,et al.  Evaluation of Circulating YKL-40 Levels in Idiopathic Interstitial Pneumonias , 2014, Lung.

[20]  C. Ban,et al.  Increased lung cancer risk in patients with interstitial lung disease and elevated CEA and CA125 serum tumour markers , 2014, Respirology.

[21]  R. Scorza,et al.  Carbohydrate antigen 15.3 as a serum biomarker of interstitial lung disease in systemic sclerosis patients. , 2013, European journal of internal medicine.

[22]  A. Fischer,et al.  Interstitial lung disease in connective tissue disorders , 2012, The Lancet.

[23]  Cynthia S Crowson,et al.  Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study. , 2010, Arthritis and rheumatism.

[24]  R. Elashoff,et al.  Surfactant Protein D and KL-6 as Serum Biomarkers of Interstitial Lung Disease in Patients with Scleroderma , 2009, The Journal of Rheumatology.

[25]  B. Hellmich,et al.  Interstitial lung disease in polymyositis and dermatomyositis , 2005, Current rheumatology reports.

[26]  Shinichi Sato,et al.  Comparative study of serum surfactant protein-D and KL-6 concentrations in patients with systemic sclerosis as markers for monitoring the activity of pulmonary fibrosis. , 2004, The Journal of rheumatology.

[27]  R. Wong,et al.  CA15-3 and cancer associated serum antigen assays are alternatives to the KL-6 assay for measuring serum MUC-1 levels in patients with interstitial lung disease associated with polymyositis/dermatomyositis. , 2002, The Journal of rheumatology.

[28]  N. Kohno,et al.  Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. , 2002, American journal of respiratory and critical care medicine.

[29]  J. Fujita,et al.  Elevated serum and BAL cytokeratin 19 fragment in pulmonary fibrosis and acute interstitial pneumonia. , 1999, The European respiratory journal.

[30]  S. Kudoh,et al.  CYFRA 21-1, a cytokeratin subunit 19 fragment, in bronchoalveolar lavage fluid from patients with interstitial lung disease. , 1998, Clinical science.