Circulating thymus and activation-regulated chemokine/CC chemokine ligand 17 is a strong candidate diagnostic marker for interstitial lung disease in patients with malignant tumors: a result from a pilot study

Abstract

Introduction

Serum Krebs von den Lungen-6 (KL-6) level is an established diagnostic marker of interstitial lung disease (ILD). However, it is also elevated in patients with non-small cell lung cancer (NSCLC). The significance of circulating thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17) in malignant diseases remains unknown.

Methods

We measured circulating TARC/CCL17 and KL-6 using enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, respectively, in 26 patients with malignant disease and six patients with benign lung disease (BLD). The cutoff levels were 500 U/mL for KL-6 and 450 pg/mL for TARC/CCL17. The significance of the markers was evaluated in relationship to the presence of ILD (n=10). The statistical significance was set at P<0.05.

Results

The KL-6 positive ratio was significantly higher in the patients with NSCLC (n=17) than in those with BLD. There was a significant difference in the KL-6 positive ratio between the patients with NSCLC without ILD and those with BLD without ILD. However, there were no significant differences in the TARC/CCL17 positive ratio between the patients with NSCLC and BLD or between those with NSCLC without ILD and those with BLD without ILD. The TARC/CCL17 positive ratio was significantly higher in the patients with malignancy and ILD than in those without ILD. There was also a significant difference in the TARC/CCL17 positive ratio between the patients with NSCLC without ILD and those with ILD.

Conclusion

TARC/CCL17 may be useful for the diagnosis of ILD in patients with malignancies. Confirmation of the results is warranted through a large-scale study.

Keywords:

• thymus and activation-regulated chemokine/CC chemokine ligand 17
• Krebs von den Lungen-6
• interstitial lung disease
• biomarker

Supplementary materials

Figure S1 ROC curve of each marker.

Notes: The value of the area under the ROC curve was <0.7 for KL-6, SP-D, and SP-A and >0.7 (0.861) for TARC/CCL17. TARC/CCL17 was thought to have a moderate accuracy to detect ILD.

Abbreviations: ROC, receiver-operating characteristic; KL-6, Krebs von den Lungen-6; SP-D, surfactant protein-D; SP-A, surfactant protein-A; TARC/CCL17, thymus and activation-regulated chemokine/CC chemokine ligand 17; ILD, interstitial lung disease.

Table S1 The relationship between average concentration of KL-6, SP-A, SP-D and TARC/CCL17 in healthy volunteers and benign lung disease in this study

Table S2 Uni-and multivariate analysis in this study

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Acknowledgments

This work was supported in whole by a research project grant, 24-B-67, from the Kawasaki Medical School.

Author contributions

All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

We declare that no conflicts of interest exist, including any financial and personal relationships with other people or organizations that could inappropriately influence our work.