Dikkopf-1 as a Novel Serologic and Prognostic Biomarker for Lung and Esophageal Carcinomas

Abstract

Gene expression profile analysis of lung and esophageal carcinomas revealed that Dikkopf-1 (DKK1) was highly transactivated in the great majority of lung cancers and esophageal squamous cell carcinomas (ESCC). Immunohistochemical staining using tumor tissue microarrays consisting of 279 archived non-small cell lung cancers (NSCLC) and 280 ESCC specimens showed that a high level of DKK1 expression was associated with poor prognosis of patients with NSCLC as well as ESCC, and multivariate analysis confirmed its independent prognostic value for NSCLC. In addition, we identified that exogenous expression of DKK1 increased the migratory activity of mammalian cells, suggesting that DKK1 may play a significant role in progression of human cancer. We established an ELISA system to measure serum levels of DKK1 and found that serum DKK1 levels were significantly higher in lung and esophageal cancer patients than in healthy controls. The proportion of the DKK1-positive cases was 126 of 180 (70.0%) NSCLC, 59 of 85 (69.4%) SCLC, and 51 of 81 (63.0%) ESCC patients, whereas only 10 of 207 (4.8%) healthy volunteers were falsely diagnosed as positive. A combined ELISA assays for both DKK1 and carcinoembryonic antigen increased sensitivity and classified 82.2% of the NSCLC patients as positive whereas only 7.7% of healthy volunteers were falsely diagnosed to be positive. The use of both DKK1 and ProGRP increased sensitivity to detect SCLCs up to 89.4%, whereas false-positive rate in healthy donors was only 6.3%. Our data imply that DKK1 should be useful as a novel diagnostic/prognostic biomarker in clinic and probably as a therapeutic target for lung and esophageal cancer. [Cancer Res 2007;67(6):2517-25]

LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis

“…Thereby, Dkk1 might be the key factor for promoting tumour metastasis by downregulating membrane LRP5/6. Notably, cancer patients with Dkk1 upregulation have long been known to have poorer prognosis, although the reason remains unknown 37 . Our present findings also show a higher expression of Dkk1 in 4T1-implanted primary tumour than metastases, and no expression of Dkk1 was detected in neighbouring normal lung tissues ( Supplementary Fig.…”

Plasma and vitreous fluid levels of Dickkopf-1 in patients with diabetic retinopathy

“…11 DKK-1 is a secreted protein and readily detectable in the circulation. [12][13][14][15][16] Therefore, it is hypothesized that DKK-1 levels in circulation or ocular fluid could be associated with the development and progression of DR.…”

Assessing the Diagnostic Value of Serum Dickkopf-related Protein 1 Levels in Cancer Detection: a Case-control Study and Meta-analysis

“…As a secreted protein, DKK1 is elevated in serum from patients with diverse malignancies. In lung cancer, DKK1 was found to be a novel serologic and histochemical biomarker, as well as a therapeutic target (Yamabuki et al, 2007). Shen et al found DKK1 to be elevated in hepatocellular carcinoma, where it complemented measurement of AFP in the diagnosis of HCC (Shen et al, 2012).…”

“…Next, the 35 remaining full manuscripts were retrieved for detailed evaluation. Finally, 10 manuscripts in total (Yamabuki et al, 2007;Jiang et al, 2009;Sheng et al, 2009;Sato et al, 2010;Shen et al, 2010;Soydinc et al, 2011;Tung et al, 2011;Lee et al, 2012;Shen et al, 2012;Shi et al, 2013), which consisted of 11 studies, were included for evaluation according to the inclusion and exclusion criteria. The remaining 25 studies were excluded because of: a) lack of sufficient data (n=5); b) duplicate publications (n=12); c) lack of a control group (n=3); d) being a review article (n=2); or e) printed in Chinese (n=3).…”

“…Some studies showed that DKK1 levels have also been associated with cancer progression and poor prognosis. DKK1 is overexpressed in prostate, lung, esophageal, and hepatic cancers, and, in these diseases, it may serve as a serologic and prognostic biomarker (Yamabuki et al, 2007). DKK1 is frequently Xiao-Ting Jiang 1& , Ying-Yu Ma 2& , Kun Guo 3 , Ying-Jie Xia 2 , Hui-Ju Wang 2 , Li Li 2 , Xu-Jun He 2 , Dong-Sheng Huang 4 *, Hou-Quan Tao 2,4 * overexpressed in ovarian carcinoma and involved in tumor invasion and progression (Wang and Zhang, 2011).…”