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

Abstract

PurposeThis 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 designEpitope 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).ResultsFour 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).ConclusionIdentified 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.

Expression and Role of Dickkopf-1 (Dkk1) in Tumors: From the Cells to the Patients

“…And followed up for 3 years. 28 Serum Dkk1 levels were quantified and analyzed in 470 patients with NSCLC (140 bone metastases, 178 extraosseous metastases and 152 complete remission). 29 Yes Yes Yes Yes Dkk1 promotes VM formation by inducing EMT-related proteins and developing CSC properties in NSCLC.…”

“…Shen et al 28 measured the serum levels of Dkk1 autoantibodies in 206 patients with NSCLC and 99 healthy controls by indirect ELISA. The patients were followed up for 3 years to evaluate the correlation between the serological level of antibodies and the overall survival time (OS) and progression-free survival (PFS).…”

The clinical significance of CXCL5 in non-small cell lung cancer

“… 40 , 41 Various biomarkers have been explored for diagnosis, targeted therapy, or prognosis. 42 – 45 CXCL5 is a member of a proangiogenic subgroup of the CXC-type chemokine family. Emerging evidence has demonstrated that CXCL5 is involved in carcinogenesis and cancer progression.…”

<p>The Clinical Diagnostic and Prognostic Value of Dickkopf-1 in Cancer</p>

“…43 Also, our team have confirmed the diagnostic value of DKK1 autoantibodies in non-small cell lung cancer. 44 In summary, DKK1 has been considered as a novel serologic diagnostic marker of cancer. And in some cancers, DKK1 combined with DKK1 antibodies could improve diagnostic value.…”

“…Also, their team further clarified the clinical significance of seroautoantibodies and evaluated their feasibility in immunological diagnosis and prognosis. 44 Cox regression analysis showed that anti-pepB antibody was considered as an independent prognostic factor of non-small cell lung cancer, suggesting that Pep B antibody subtype was the most valuable biomarker with good prognosis in NSCLC. Whether such unique epitopes can be found in other cancer types, and whether such a method can be used to diagnose cancer, needs further exploration.…”