DKK-1 in prostate cancer diagnosis and follow up

Abstract

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.

Bone turnover markers in serum and urine as diagnostic, prognostic and monitoring biomarkers of bone metastasis

“…Serum sclerostin values increased in prostate cancer patients with bone metastases by about 40% in comparison to a control group of age-adjusted men [43]. DKK-1 values were not different in 159 men who were diagnosed with cancer or cancer free by prostate biopsy [149]. However, patients who developed bone metastases in the follow-up were characterized by reduced DKK-1 values.…”

Dickkopf-related protein 1 induces angiogenesis by upregulating vascular endothelial growth factor in the synovial fibroblasts of patients with temporomandibular joint disorders

“…DKK family members are implicated in various developmental, pathological, and physiological processes ( 16 , 27 ). In prostate cancer, DKK-1 acts as a marker of carcinogenesis, and may provide a novel method of prostate cancer prediction for patients with negative primary biopsy results, who may otherwise progress to bone metastasis ( 28 ). Recent studies have demonstrated that overexpression of DKK-1 may be associated with increased angiogenesis ( 14 , 15 ).…”

Therapeutic potency of Wnt signaling antagonists in the pathogenesis of prostate cancer, current status and perspectives

“…The role of DKK1 expression in prostate cancer cell lines have been investigated in several previous studies (Browne et al, 2016;D'Amelio et al, 2014;Hall, Bafico, Dai, Aaronson, & Keller, 2005;Hall, Daignault, Shah, Pienta, & Keller, 2008;Hall et al, 2010;Li et al, 2008b;Thudi et al, 2011). The expression of DKK-1 regulates Wnt-induced osteoblastic activity in prostate cancer cell lines.…”

“…They reported that DKK‐1 perform worse than prostate‐specific antigen (PSA) in the early diagnosis of prostate cancer, but better than PSA in detecting patients who developed prostate cancer during follow‐up. Thus, the authors concluded that DKK‐1 could be a good predictive marker for prostate cancer development and prognosis of bone metastases (D’Amelio et al, ). Taken together, it seems that DKK1 could be a key inhibitory factor for therapeutic intervention in osteoblastic metastases during prostate cancer.…”