High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients

Rachner, Tilman D.; Thiele, Stefanie; Göbel, Andy; Browne, Andrew; Fuessel, Susanne; Erdmann, Kati; Wirth, Manfred P.; Fröhner, M.; Todenhöfer, Tilman; Muders, Michael H.; Kieslinger, Matthias; Rauner, Martina; Hofbauer, Lorenz C.

doi:10.1186/1471-2407-14-649

Cited by 66 publications

(58 citation statements)

References 16 publications

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“…This finding may indicate that absence of Wnt pathway inhibition by DKK-1 promotes oncogenesis, an idea supported by previous data showing that modulators of bone turnover can be altered not only in metastatic disease but also during early stages of tumor progression [7,13]. Liang et al also observed lower median DKK-1 level in PC patients compared to controls [14].…”

Section: Disease Markerssupporting

confidence: 55%

“…However, this finding failed to meet statistical significance. Data regarding differences of DKK-1 in BPH and PC are scarce and partially discrepant [13]. Our findings, together with the lack of correlation between DKK-1 tissue expression and DKK-1 serum levels, may be explained by the hypothesis that PC tissue-derived DKK-1 only modestly influences systemic serum DKK-1 levels [13].…”

Section: Disease Markersmentioning

confidence: 60%

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114 Systemic alterations of Wnt Inhibitors in patients with prostate cancer and bone metastases

Todenhöfer¹,

Leidenberger²,

Hennenlotter³

et al. 2014

European Urology Supplements

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Purpose. Dickkopf-1 (DKK-1) and sclerostin seem to inhibit osteoblast activity by blocking the Wnt pathway, which leads to progression of metastatic prostate cancer (PC). However, it is unknown whether serum levels of these proteins are altered in PC patients with or without metastasis. The aim of this study was to assess DKK-1 and sclerostin serum levels in PC patients, including patients with bone metastases. Methods. The study cohort (N = 143) consisted of 53 controls with benign prostatic hyperplasia (BPH), 43 with localized PC (PC cM0), and 47 had PC with metastasis (PC cM1). Serum levels of DKK-1 and sclerostin were measured by enzyme-linked immunosorbent assay. Results were compared using the Kruskal-Wallis tests; post hoc analysis was performed using the Tukey-Kramer test. Results. Mean DKK-1 levels in patients with BPH (2809.4 pg/ml) (p < 0 001) as well as PC cM1 (2575.5 pg/ml) (p = 0 001) were significantly higher than in patients with PC cN0 cM0 (1551.8 pg/ml). Among PC cM1 patients, median DKK-1 levels were significantly lower in patients with castration-resistant disease compared to those with hormone-sensitive PC (p = 0 02); in contrast, sclerostin concentrations were elevated (p = 0 04). DKK-1 correlated with PSA in the cM1 group (p = 0 03) and sclerostin correlated with PSA in the PC group (0.01). Conclusions. DKK-1 is involved in the progression of PC. DKK-1-mediated inhibition of osteoblasts, which contributes to tumor progression and osteolytic metastases, may also play a role in the development of metastases with osteoblastic features. The use of DKK-1 antibodies should be considered for studies including metastatic PC patients.

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Section: Disease Markerssupporting

confidence: 55%

Section: Disease Markersmentioning

confidence: 60%

114 Systemic alterations of Wnt Inhibitors in patients with prostate cancer and bone metastases

Todenhöfer¹,

Leidenberger²,

Hennenlotter³

et al. 2014

European Urology Supplements

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“…In some cases, the expression of DKK-1 has been shown to be upregulated in various kinds of cancers. Rachner et al (2014) showed that both tissue and serum DKK-1 levels were significantly higher in prostate cancer patients compared with healthy controls. In addition, high serum DKK-1 levels were shown to be an independent prognostic factor for prostate cancer, suggesting that DKK-1 might act as an oncogene in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of serum DKK-1 predicts poor prognosis in patients with papillary thyroid cancer

Zhao¹,

Wang²,

Wang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The Wnt inhibitor dickkopf-1 (DKK-1) has been shown to be closely correlated with tumor initiation and progression in various types of cancers. However, the serum level of DKK-1 in patients with papillary thyroid cancer (PTC) and its potential clinical significance is poorly understood. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the level of serum DKK-1 in patients with PTC (N = 132) and healthy controls (N = 40). The association between serum DKK-1 level and clinicopathological parameters of PTC was examined and independent prognostic markers for PTC were identified. The mean serum DKK-1 level was significantly lower in patients with PTC than healthy controls (44.64 ± 15.13 and 85.51 ± 9.94 ng/mL, respectively; P < 0.01). Following treatment, the mean serum DKK-1 level in PTC patients significantly increased (67.03 ± 17.09 ng/mL; P < 18887 Prognostic value of serum DKK-1 in papillary thyroid cancer ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 18886-18894 (2015) 0.01). Serum DKK-1 level was associated with various PTC clinical features including tumor size (P = 0.003), lymph node metastasis (P = 0.001), and tumor-node-metastasis stage (P = 0.004). Survival analysis revealed that PTC patients who had lower serum DKK-1 levels suffered both poorer overall survival (P = 0.036) and relapse-free survival (P = 0.015). Moreover, serum DKK-1 levels were an independent risk factor for predicting the prognosis of PTC (P = 0.031). In conclusion, low DKK-1 serum levels are associated with poor prognosis in PTC patients and DKK-1 could potentially be used as a biomarker leading to earlier diagnosis of PTC.

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“…At present, there are numerous molecular markers for the evaluation of the prognosis of prostate cancer, such as auxin, vascular endothelial growth factor, and transforming growth factor beta 1, etc. These provide effective references for the clinical treatment and prognosis of prostate cancer (Rachner et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Expression and significance of S100P, CD147, and OCT4 in different prostate cancer tissue TNM stages

Wang¹,

Zhang²,

Wang³

2015

Genet. Mol. Res.

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ABSTRACT. The aim of this project was to investigate the expression and significance of S100P, CD147, and OCT4 in prostate cancer tissue at different TNM stages. We enrolled 54 patients with prostate cancer, 40 with benign prostatic hyperplasia, and 20 subjects with normal prostates. S100P, CD147, and OCT4 were detected by immunohistochemistry. The positive rate of S100P detection was 18.52% in prostate cancer tissues, significantly lower than in normal and benign prostate hyperplasia tissues (P ˂ 0.05). The positive expression rate of CD147 and OCT4 were 100 and 77.38% in prostate cancer tissue, respectively, both markedly higher than in normal and benign prostate hyperplasia tissue (P ˂ 0.05). The positive rate of S100P in stage V was 0, which was significantly lower than in stages I (37.50%) and II (35.71%) (P ˂ 0.05). OCT4 expression in stages III (86.67%) and V (94.12%) was higher than in stage I (37.50%). The positive rate of S100P in patients with distant metastasis was 4%, which was significantly lower than that in patients without metastases 6845 S100P, CD147, and OCT4 in prostate cancer ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6844-6851 (2015) (P ˂ 0.05). In contrast, the positive rate of OCT4 in patients with distant metastasis was 92%. S100P, CD147, and OCT4 expression in prostate cancer patients with different degrees of differentiation had no significant difference (P > 0.05). Overall, our results demonstrated that S100P expression in prostate cancer tissue was significantly decreased, whereas CD147 and OCT4 expression was increased. Their expression levels were closely associated with TNM stage and distant metastasis, but were not related to the degree of differentiation.

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High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients

Cited by 66 publications

References 16 publications

114 Systemic alterations of Wnt Inhibitors in patients with prostate cancer and bone metastases

114 Systemic alterations of Wnt Inhibitors in patients with prostate cancer and bone metastases

Downregulation of serum DKK-1 predicts poor prognosis in patients with papillary thyroid cancer

Expression and significance of S100P, CD147, and OCT4 in different prostate cancer tissue TNM stages

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