Clinical Chemistry
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Clinical Chemistry 55: 1656-1664, 2009. First published July 23, 2009; 10.1373/clinchem.2009.125641
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(Clinical Chemistry. 2009;55:1656-1664.)
© 2009 American Association for Clinical Chemistry, Inc.

Cancer Diagnostics

Clinical Significance and Prognostic Value of Serum Dickkopf-1 Concentrations in Patients with Lung Cancer

Shi Le Sheng1,2, Gang Huang1,2,a, Bin Yu3 and Wen Xin Qin3,a

1 Department of Nuclear Medicine, Renji hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;2 Institute of Health Sciences, SIBS, CAS and SJTUSM, Shanghai, China;3 National Laboratory for Oncogenes and Related Genes, WHO Collaborating Center for Research on Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University Medical School, Shanghai, China.

aAddress correspondence to: G.H. at Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No.1630 Dong Fang Road, Shanghai 200127, China. Fax +86-21-63111384; e-mail huang2802{at}163.com. W.X.Q. at National Laboratory for Oncogenes and Related Genes, WHO Collaborating Center for Research on Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University Medical School, Shanghai 200032, China. Fax +86-21-64436581; e-mail wxqin{at}sjtu.edu.cn.

Background: Dickkopf-1 (DKK1), a secreted protein, is known as a negative regulator of the Wnt signaling pathway, which has been implicated in the development of several types of cancers. Clinical significance of serum DKK1 in lung cancer remains to be determined.

Methods: A novel time-resolved immunofluorometric assay was developed. By use of this method, we investigated the serum concentrations of DKK1 in 592 patients with malignancies, 72 patients with benign lung disease, and 120 healthy controls. Serum cytokeratin 19 fragment and neuron-specific enolase values were obtained.

Results: Serum DKK1 concentrations were significantly higher in patients with lung cancer than in patients with other malignant tumors or benign lung diseases and healthy controls. Serum concentrations of DKK1 were decreased significantly in groups of patients with gastric cancer, colorectal cancer, ovarian cancer, and cervical adenocarcinoma compared with healthy controls. Application of both DKK1 and cytokeratin 19 fragment increased sensitivity, correctly identifying 89.6% of the non–small cell lung cancer patients as positive. The use of both DKK1 and neuron-specific enolase increased sensitivity to detect small cell lung cancer to 86.2%. DKK1 concentrations increased with stage, tumor class, and presence of lymph node and distant metastases, regardless of histology and patient age and sex. Patients with a DKK1 concentration of 22.6 µg/L or higher had a statistically significantly diminished survival compared with patients whose DKK1 values were lower.

Conclusions: DKK1 was preferentially expressed in lung cancer. Increasing concentrations of DKK1were significantly associated with tumor progression and decreased survival in patients with lung cancer. .






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Copyright © 2009 by the American Association for Clinical Chemistry.