Serum concentrations of DKK‐1 correlate with the extent of bone disease in patients with multiple myeloma

Kaiser, Martin; Mieth, Maren; Liebisch, Peter; Oberländer, Romy; Rademacher, Jessica; Jakob, Christian; Kleeberg, Lorenz; Fleissner, Claudia; Braendle, Edgar; Peters, Malte; Stover, David R.; Sezer, Orhan; Heider, Ulrike

doi:10.1111/j.1600-0609.2008.01065.x

Cited by 144 publications

(101 citation statements)

References 25 publications

(40 reference statements)

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“…It is reported that alterations of circulating DKK-1 protein levels have been shown to be associated with various diseases such as multiple myeloma, rheumatoid arthritis, breast cancer, lung cancer, and esophageal cancer patients. [12][13][14][15][16] However, there is no documented study to associate circulating DKK-1 levels with DR. There is also no information available concerning the DKK-1 level in the vitreous fluid.…”

Section: Discussionmentioning

confidence: 99%

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

Qiu

Yan

et al. 2014

Eye

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Purpose Dickkopf-1 (DKK-1) is a secreted inhibitor of the Wnt/b-catenin signaling pathway, which plays a pathogenic role in diabetic retinopathy (DR). We aimed to investigate whether DKK-1 levels in the plasma and the vitreous are associated with DR in type 2 diabetes mellitus (DM) patients. Methods Case-control study: plasma samples were collected from 125 type 2 DM including 81 DR (29 non-proliferative DR (NPDR) and 52 proliferative DR (PDR)), 44 non-DR patients (NDR), and 100 non-diabetic controls. Undiluted vitreous fluid samples were obtained from 30 PDR and 25 nondiabetic patients. DKK-1 concentrations in samples were determined using enzymelinked immunosorbent assay. Variables were compared with the Kruskal-Wallis H test, Mann-Whitney U-test, and w 2 -test, when appropriate. Results Plasma DKK-1 levels were significantly lower in DR patients (median: 465.77 pg/ml, range: 137.11-1190.31) than in non-diabetic controls (656.83 pg/ml, 171.63-1795.08; Po0.001) and NDR patients (693.04 pg/ml, 305.43-1218.35; Po0.001). Furthermore, DKK-1 levels were lower in PDR patients (425.21 pg/ml, 137.10-1077.32) compared with NPDR patients (594.86 pg/ml, 256.36-1393.27; P ¼ 0.003). Vitreous absolute DKK-1 levels in PDR patients (259.04 pg/ml, 104.44-596.96) were higher than in nondiabetic controls (138.26 pg/ml, 18.69-239.52; Po0.001). After normalizing by total vitreous protein concentrations, however, there was no significant difference between the groups. DKK-1 levels in vitreous were lower than those in plasma in both groups (Po0.001 for controls; P ¼ 0.002 for PDR patients).Conclusions Decreased plasma DKK-1 levels, which may contribute to the Wnt pathway activation, are associated with the presence and progression of DR, and have potential to become a biomarker for DR.

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Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Qiu

Yan

et al. 2014

Eye

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“…On the other hand, high levels of DKK1 in patients' serum are associated with poor prognosis in various cancers including oesophageal squamous cell carcinoma [136] , lung cancer [137] , breast cancer [138] and cervical cancer [138] , suggesting that the serum level of DKK1 may also reflect the prognosis of HCC patients. In multiple myeloma, high DKK1 serum levels are associated with osteolytic bone lesions [139] and patients responding to anti-myeloma treatment show a decrease in DKK1 serum levels [140] , suggesting the involvement of DKK1 in this aspect. Recently, Fulciniti et al [141] evaluated the effect of anti-DKK1 monoclonal antibody (BHQ880) in a multiple myeloma mouse model and found that it induced bone formation and inhibited tumour-induced osteolytic bone lesions.…”

Section: Dkk1mentioning

confidence: 99%

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

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Liver cancer is the fifth and seventh most common cause of cancer in men and women, respectively. Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC). Based on the current understanding, this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs (DKKs) in regulating Wnt/β-catenin signalling, which is poorly understood and understudied. DKKs are a family of secreted proteins that comprise at least four members, namely DKK1-DKK4, which act as inhibitors of Wnt/β-catenin signalling. Nevertheless, not all members antagonize Wnt/β-catenin signalling. Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis. Because of the important oncogenic roles, there are an increasing number of therapeutic molecules targeting β-catenin and the Wnt/ β-catenin pathway for potential therapy of HCC. hepatocellular carcinoma anD the unmet meDical neeDSLiver cancer ranks the fifth most common cancer in men and the second leading cause of cancer-related death. In women, it is the seventh most frequent cancer and sixth leading cause of cancer death [1] . Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver. Men are three times more likely to develop HCC than women and the incidence increases with age [2] . HCC is prevalent in Asia and Africa, but recently it is on the rise in the Western world due to an increase in hepatitis C virus (HCV) infection [3] . Risk factors for HCC include chronic hepatitis B virus (HBV) and HCV infections, cirrhosis, chronic alcohol abuse, aflatoxin ingestion, non-alcoholic steatohepatitis and other metabolic liver diseases [4,5] . Much of HCC occurs in the background of cirrhosis. About 80%-90% of patients with cirrhosis go on to develop HCC eventually and the remaining 10%-20% of cases develop HCC without cirrhosis. Furthermore, HBV and HCV infections increase the risk of developing cirrhosis and later HCC. Among the HCC

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“…85 Bone marrow plasma Dkk-1 levels were increased in MM patients, and associated with Dkk-1 concentrations in peripheral blood, levels of Dkk-1 transcripts in myeloma cells and the presence of osteolytic lesions. [86][87][88] Gene expression studies in 171 newly diagnosed MM patients showed that overexpression of Dkk-1 correlated with the degree of osteolytic bone disease. 89 Similarly, serum Dkk-1 levels were elevated in myeloma patients with lytic bone disease compared with those without lytic lesions by conventional radiography, and also correlated with the number of bone lesions.…”

Section: Correlations Of Bone Turnover Markers With Myeloma Activity mentioning

confidence: 99%

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

et al. 2010

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Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during antimyeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino-and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.

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Serum concentrations of DKK‐1 correlate with the extent of bone disease in patients with multiple myeloma

Cited by 144 publications

References 25 publications

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

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

Dickkopfs and Wnt/β-catenin signalling in liver cancer

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

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