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Combined detection of dickkopf-1 subtype classification autoantibodies as biomarkers for the diagnosis and prognosis of non-small cell lung cancer

Authors Shen L, Wu X, Tan J, Gu M, Teng Y, Wang Z, Yue W

Received 7 February 2017

Accepted for publication 21 April 2017

Published 18 July 2017 Volume 2017:10 Pages 3545—3556

DOI https://doi.org/10.2147/OTT.S134162

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Lei Shen,1,* Xiaoguang Wu,2,* Jinjing Tan,1 Meng Gu,1 Yu Teng,1 Zitong Wang,3 Wentao Yue1,4

1Department of Cellular and Molecular Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, 2Department of Ward 2, 3Department of Thoracic Surgery, Beijing Chest Hospital, Beijing, 4Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang, Beijing, People’s Republic of China

*These authors contributed equally to this work

Purpose: This study aims to identify the clinical significance of serum autoantibodies against dickkopf-1 (DKK1) and evaluate their feasibility in the immunodiagnosis and prognosis of non-small cell lung cancer (NSCLC).
Experimental design: Epitope mapping by peptide microarray-based serum screening of NSCLC patients (n=72) and healthy controls (n=16) was performed. Indirect ELISA with peptides was used to measure the serum levels of autoantibodies in 206 NSCLC patients and 99 healthy controls. A 3-year follow-up was monitored to evaluate the correlation between serological levels of autoantibodies and overall survival (OS) and progression-free survival (PFS).
Results: Four highly reactive epitopes were identified, which included peptides 67–84 (Pep A), 37–54 (Pep B), 145–156 (Pep C) and 247–261 (Pep D). The autoantibodies levels were considerably higher in sera of NSCLC patients compared with controls (P<0.001), and a highly significant correlation with distant metastases was observed (Pep A: P=0.09, Pep B: P<0.01, Pep C: P<0.01 and Pep D: P<0.01). High levels of antibody subtype to Pep B were remarkably associated with better OS (P=0.004) and PFS (P=0.006). Subsequent Cox regression analysis disclosed that antibody to Pep B was an independent prognostic factor for NSCLC (OS: P=0.008, HR =0.435, 95% CI 0.236–0.802; PFS: P=0.032, HR =0.533, 95% CI 0.322–0.950).
Conclusion: Identified linear epitopes of antigens by peptide microarray are easily available, and subtype classification of DKK1 autoantibodies as novel biomarkers for the diagnosis and prognosis of NSCLC. Our results also highlight the antibody subtype to Pep B as the most valuable biomarker for favorable prognosis of NSCLC.

Keywords: dickkopf-1, DKK1, autoantibodies, NSCLC, tumor immunity, antigenic sites

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