128P - Serum DKK-1 as a clinical and prognostic factor in non-small cell lung cancer patients with bone metastases

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Thoracic Malignancies
Non-Small Cell Lung Cancer
Presenter rong Qiao
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors R. Qiao1, T. Chu1, B. Han1, R. Zhong1, Q. Chang2, J. Teng1, J. Pei1
  • 1Department Of Pulmonary Medicine, Shanghai Chest Hospital, 200030 - Shanghai/CN
  • 2Shanghai Jiao Tong University School of Medicine, Shanghai/CN

Abstract

Background

The Wnt/β-catenin pathway plays a crucial role in tumor pathogenesis, specifically in cell proliferation, angiogenesis, motility and invasiveness. The activity of Wnt family ligands is antagonized by several secreted factors including Dickkopf (DKK). A member of the Dickkopf family, DKK-1, is a 35 kDa secreted protein that is a potent inhibitor of Wnt/β-catenin signaling. The study was designed to evaluate the association between serum Dickkopf-1(DKK-1) and non- small cell lung cancer(NSCLC) bone metastases.

Methods

Serum DKK-1and CEA levels were quantified in 318 NSCLC patients, 140 with osseous metastases and 178 with extraosseous metastases. We used receiver operating characteristics (ROC) to evaluate the predictive qualities of these parameters for bone metastases.

Results

Serum DKK-1 levels were significantly higher in patients with osseous metastases compared with patients with extraosseous metastases (P < 0.001). ROC curves showed that the optimum cutoff was 311.8 ng/ml (area under curve [AUC] 0.791, 95% confidence interval [CI] 0.739–0.843, sensitivity 77.1% and specificity 71.4%). ROC analysis also showed that testing both DKK-1 and CEA increased the detection accuracy for NSCLC bone metastases compared with CEA alone (AUC 0.797, 95% CI 0.746–0.848, sensitivity 82.9% and specificity 68.9%; DKK-1 plus CEA vs. DKK-1 alone P = 0.370; DKK-1 plus CEA vs. CEA alone P = 0.0001). Thus, serum DKK-1 correlated with the number of bone lesions (P = 0.042). In osseous metastases group, Kaplan–Meier analysis showed that patients with high serum DKK-1 levels had poorer overall survival than patients with low serum DKK-1 levels (P = 0.025), and multivariable analyses showed serum DKK-1 to be an independent prognostic factor for overall survival (P = 0.029).

Conclusions

Our data shows that serum DKK-1 levels are increased in NSCLC patients with bone metastases. More importantly this is the first report to show that high serum DKK-1 levels are associated with the extent of bone metastases and poor survival in NSCLC patients with bone metastases.

Clinical trial identification

Legal entity responsible for the study

Shanghai Chest Hospital

Funding

The Science and Technology Development Fund of Shanghai Chest Hospital (Grant No. 2014YZDC10101)

Disclosure

All authors have declared no conflicts of interest.