Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population

Zheng, Muhan; Aiju, Lou; Zhang, Haoru; Zhu, Shijie; Yang, Min; Wei, Lai

doi:10.1007/s40744-021-00288-x

Cited by 44 publications

(34 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 22 Zheng et al reported that the serum levels of CA19-9, CA125 and CEA were also elevated in RA-ILD and showed a strong association with the severity of the disorder. 16 Similarly, Shi et al showed that SS-ILD patients had elevated serum levels of tumor markers, including NSE, CEA, CA125, and CA153, 18 while Wong et al reported that IM-ILD patients without cancer had elevated levels of CA153. 19 Sargin et al considered that RA patients with an increase in tumor markers especially CA153 and CA125 should be suspected of having an ILD.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Bao

Zhang

Shi

et al. 2021

IJGM

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

“… 14 , 15 The value of tumor markers for investigating ILDs has also been supported by the findings of several recent studies, especially for diagnosing and evaluating the risk of developing this condition. 16–20 …”

Section: Introductionmentioning

confidence: 99%

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

Bao

Zhang

Shi

et al. 2021

IJGM

View full text Add to dashboard Cite

show abstract

“…Even the tumour markers CA (carbohydrate antigen)-125 and CA19-9 have been studied as markers of epithelial damage and can predict short-term mortality [ 40 ]. Similarly, in RA-ILD, CA125, CA19-9, CEA (carcinoembryonic antigen), and KL-6 have been validated as biomarkers [ 41 ]. Other biomarkers for RA-ILD can include genetic polymorphisms of the MUC5B gene and serum interleukin-13 levels [ 20 , 42 ].…”

Section: Screening Monitoring and Diagnosismentioning

confidence: 99%

Management of Connective Tissue Disease–related Interstitial Lung Disease

Ahmed

Handa

2022

Curr Pulmonol Rep

View full text Add to dashboard Cite

Purpose of Review This review aims to collate current evidence on the screening, diagnosis, and treatment of various connective tissue disease (CTD)–associated interstitial lung diseases (CTD-ILD) and present a contemporary framework for the management of such patients. It also seeks to summarize treatment outcomes including efficacy and safety of immunosuppressants, anti-fibrotics, and stem cell transplantation in CTD-ILD. Recent Findings Screening for ILD has been augmented by the use of artificial intelligence, ultra-low dose computerized tomography (CT) of the chest, and the use of chest ultrasound. Serum biomarkers have not found their way into clinical practice as yet. Identifying patients who need treatment and choosing the appropriate therapy is important to minimize the risk of therapy-related toxicity. The first-line drugs for systemic sclerosis (SSc) ILD include mycophenolate and cyclophosphamide. Nintedanib, an anti-fibrotic tyrosine kinase inhibitor, is approved for use in SSc-ILD. The US Food and Drug Administration (FDA) has recently approved tocilizumab subcutaneous injection for slowing the rate of decline in pulmonary function in adult patients with SSc-ILD. Autologous stem cell transplantation may have a role in select cases of SSc-ILD. Summary CTD-ILD is a challenging area with diverse entities and variable outcomes. High-resolution CT is the investigative modality of choice. Treatment decisions need to be individualized and are based on patient symptoms, lung function, radiologic abnormalities, and the risk of disease progression. Precision medicine may play an important role in determining the optimal therapy for an individual patient in the future.

show abstract

“…Additionally, the development of tumor markers may also contribute to ILD; their diagnostic utilities have been investigated. The levels of carbohydrate antigen (CA) 19–9, CA125, CEA, and CA15-3 were increased compared to a control group of RA-non-ILD patients [ 12 , 13 ]. D-dimer is the end-product of cross-linked fibrinolysis and is involved in the acute phase of inflammation; it may thus contribute to the pathophysiology of RA-ILD [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of biomarkers by machine learning classifiers to assist diagnose rheumatoid arthritis-associated interstitial lung disease

et al. 2022

View full text Add to dashboard Cite

Background This study aimed to search for blood biomarkers among the profiles of patients with RA-ILD by using machine learning classifiers and probe correlations between the markers and the characteristics of RA-ILD. Methods A total of 153 RA patients were enrolled, including 75 RA-ILD and 78 RA-non-ILD. Routine laboratory data, the levels of tumor markers and autoantibodies, and clinical manifestations were recorded. Univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and partial least square (PLS) were performed, and the receiver operating characteristic (ROC) curves were plotted. Results Univariate analysis showed that, compared to RA-non-ILD, patients with RA-ILD were older (p < 0.001), had higher white blood cell (p = 0.003) and neutrophil counts (p = 0.017), had higher erythrocyte sedimentation rate (p = 0.003) and C-reactive protein (p = 0.003), had higher levels of KL-6 (p < 0.001), D-dimer (p < 0.001), fibrinogen (p < 0.001), fibrinogen degradation products (p < 0.001), lactate dehydrogenase (p < 0.001), hydroxybutyrate dehydrogenase (p < 0.001), carbohydrate antigen (CA) 19–9 (p < 0.001), carcinoembryonic antigen (p = 0.001), and CA242 (p < 0.001), but a significantly lower albumin level (p = 0.003). The areas under the curves (AUCs) of the LASSO, RF, and PLS models attained 0.95 in terms of differentiating patients with RA-ILD from those without. When data from the univariate analysis and the top 10 indicators of the three machine learning models were combined, the most discriminatory markers were age and the KL-6, D-dimer, and CA19-9, with AUCs of 0.814 [95% confidence interval (CI) 0.731–0.880], 0.749 (95% CI 0.660–0.824), 0.749 (95% CI 0.660–0.824), and 0.727 (95% CI 0.637–0.805), respectively. When all four markers were combined, the AUC reached 0.928 (95% CI 0.865–0.968). Notably, neither the KL-6 nor the CA19-9 level correlated with disease activity in RA-ILD group. Conclusions The levels of KL-6, D-dimer, and tumor markers greatly aided RA-ILD identification. Machine learning algorithms combined with traditional biostatistical analysis can diagnose patients with RA-ILD and identify biomarkers potentially associated with the disease.

show abstract

Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population

Cited by 44 publications

References 29 publications

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

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

Management of Connective Tissue Disease–related Interstitial Lung Disease

Identification of biomarkers by machine learning classifiers to assist diagnose rheumatoid arthritis-associated interstitial lung disease

Contact Info

Product

Resources

About