Dickkopf-1 autoantibody is a novel serological biomarker for non-small cell lung cancer

Xiao, Yao; Jiang, Hua; Zhang, Cuizhen; Wang, Huamao; Yang, Lin; Yang, Yu; Yu, Junming; Shi, Bizhi; Shen, Zhijun; Gao, Huiping; Chen, Zhiwei; Tian, Shujun; Lu, Shun; Li, Zonghai; Gu, Jianren

doi:10.3109/13547500903325662

Cited by 23 publications

(22 citation statements)

References 27 publications

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“…This is particular important in order to increase the ability to predict PCa development; although only 13 patients developed a new cancer during follow up, the ROC analyses showed that DKK-1 performed slightly better than PSA in detecting these patients. Our results confirmed literature data reporting the role of DKK-1 as a potential serological biomarker in different tumors such as gastric cancer [26], hepatocellular carcinoma [27,28], non-small cell lung cancer [29] and gynaecological cancer [5]. …”

Section: Discussionsupporting

confidence: 91%

DKK-1 in prostate cancer diagnosis and follow up

et al. 2014

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BackgroundDickoppf-1 (DKK-1) is a negative regulator of bone formation with tumorigenic potential. The up-regulation of DKK-1 is an early event in prostate cancer (PCa) development, thus we investigated its role as a marker in the diagnosis and prognosis of PCa.MethodsWe retrospectively enrolled 159 patients who underwent prostate biopsy, either for elevated PSA or suspect digital rectal examination, between 2003 and 2010. During the biopsy, one serum sample was collected from all patients; PSA and DKK-1 were measured by ELISA technique. Amongst the biopsy of 159 patients 75 were affected by PCa and 84 were not the mean period of follow-up for these patients was 5 years; a new biopsy was performed in case of PCa suspicion.ResultsPSA performed better than DKK-1 in detecting PCa (0.63 vs 0.51 respectively). Differently from PSA DKK-1 was significantly higher in patients who developed PCa during follow-up than in cancer-free ones, thus DKK-1 performed better than PSA in detecting these patients (0.67 vs 0.55). DKK-1 was significantly lower in patients with bone metastases, whereas PSA was not significantly different in patients with different outcomes.ConclusionsDKK-1 might be predictive for patients negative at first biopsy who will develop PCa and in the prognosis of bone metastases. It performed worse than PSA in the early diagnosis of Pca.

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Section: Discussionsupporting

confidence: 91%

DKK-1 in prostate cancer diagnosis and follow up

et al. 2014

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“…A retrospective analysis of DKK1 expression showed that DKK1 was altered during PCa progression [27]. So far, only a few studies have been reported regarding the roles of DKK1 in NSCLC, mainly focusing the diagnosis and prognosis values [12,21,28-30]. The role of DKK1 in NSCLC, its mechanism of function and clinical aspects need further studies.…”

Section: Discussionmentioning

confidence: 99%

Dickkopf-1 Is Oncogenic and Involved in Invasive Growth in Non Small Cell Lung Cancer

Qin

Guo

et al. 2013

PLoS ONE

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Dickkopf-1 (DKK1) is an inhibitor of the Wnt/β-catenin signaling pathway. However, the role of DKK1 in the progression of non small cell lung cancer (NSCLC) is not fully understood. In this study, RT-PCR and Western blot were used to examine the expression of DKK1 in a panel of ten human NSCLC cell lines and NSCLC tissues. DKK1 expression was highly transactivated in the great majority of these cancer lines. The expression of DKK1 was upregulated on both mRNA and protein levels in NSCLC tissues compared with the adjacent normal lung tissues. Immunohistochemistry and immunofluoresence revealed that DKK1 was mainly distributed in the cytoplasm in both carcinoma tissues and cell lines. DKK1 protein expression was also evaluated in paraffin sections from 102 patients with NSCLC by immunohistochemistry, and 65(63.73%)tumors were DKK1 positive. Relative analysis showed a significant relationship between DKK1 positive expression and lymph node metastasis(P<0.05). Patients with DKK1-positive tumors had poorer DFS than those with negative ESCC (5-year DFS; 15.4% versus 27%, P = 0.007). To further explore the biological effects of DKK1 in NSCLC cells, we over-expressed DKK1 in NSCLC 95C cell using eukaryotic expression vector pCMV-Tab-2b and performed a knockdown of DKK1 in LTEP-a-2 cell using a short hairpin RNA expression vector pSilencer 5.1. DKK1 did not have any effect on proliferation, but seemed to play a role in migration and invasion capability. Overexpression of DKK1 promotes migratory and invasive activity of 95C, while DKK1 knockdown resulted in the suppression of migration and invasion potentials of LTEP-a-2 cell. Taken together, these results indicate that DKK1 may be a crucial regulator in the progression of NSCLC. DKK1 might be a potential therapeutic target in NSCLC.

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“…Furthermore, most of the studies have detected all immunoglobulin anti-bodies to recombinant antigens and limited studies using antigen-derived peptides with limited sample sizes have been published 10,19,20,22,23. The correlation of autoantibodies with prognosis is rather contradictory across studies.…”

Section: Discussionmentioning

confidence: 99%

“…ELISA was developed using recombinant DKK1 proteins as antigens for the detection of autoantibodies in plasma. Previous studies showed that DKK1 autoantibodies could serve as diagnostic biomarkers in NSCLC and esophageal squamous cell carcinoma 19,20. However, the association between DKK1 autoantibodies and the prognosis in cancer is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Shen¹,

Wu²,

Tan³

et al. 2017

OTT

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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.

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Dickkopf-1 autoantibody is a novel serological biomarker for non-small cell lung cancer

Abstract: Our results suggest that the detection of circulating DKK1 autoantibody could potentially serve as a useful non-invasive marker for determining lung cancer status.

Cited by 23 publications

References 27 publications

DKK-1 in prostate cancer diagnosis and follow up

DKK-1 in prostate cancer diagnosis and follow up

Dickkopf-1 Is Oncogenic and Involved in Invasive Growth in Non Small Cell Lung Cancer

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

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