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Decreased expression of Dkk1 and Dkk3 in human clear cell renal cell carcinoma
Chang-Cheng Guo1, Xiao-Long Zhang1, Bin Yang1
1Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.
Abstract:
The expression patterns of the Dickkopf (Dkk) family of proteins varies in different cancers. In the present study, the expression levels of Dkk1 and Dkk3 were investigated in clear cell renal cell carcinoma (ccRCC) tissues. Dkk1 and Dkk3 serum levels were also examined in patients with ccRCC, and the association between clinicopathological features and Dkk levels was investigated. Serum Dkk1 and Dkk3 were quantified using ELISA in 64 patients with ccRCC and in 30 healthy individuals (controls). The expression levels of Dkk1 and Dkk3 were analyzed in tumor and adjacent normal tissues obtained from patients with ccRCC (n=20) using quantitative polymerase chain reaction (qPCR), western blot analysis and immunohistochemistry. The mean serum levels of Dkk1 and Dkk3 in the patients with ccRCC were significantly lower than those in the healthy controls. Furthermore, the serum Dkk1 levels were significantly lower at higher tumor‑node‑metastasis stages and tumor grades. qPCR, western blot analysis and immunohistochemistry revealed a significant decrease in the Dkk1 and Dkk3 mRNA and protein levels in the tumor tissues compared with the adjacent normal tissues. Consequently, Dkk1 and Dkk3 may present a novel molecular target for the diagnosis and therapeutic treatment of ccRCC.
Insights
Dickkopf-1 (Dkk1) and Dickkopf-3 (Dkk3) levels are significantly lower in clear cell renal cell carcinoma (ccRCC) patients
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The Dickkopf (Dkk) protein family plays a role in various cancers.
- Expression patterns of Dkk proteins differ across cancer types.
- Dkk1 and Dkk3 roles in clear cell renal cell carcinoma (ccRCC) require further investigation.
Purpose of the Study:
- To investigate Dkk1 and Dkk3 expression levels in ccRCC tissues and serum.
- To examine the association between Dkk1/Dkk3 levels and ccRCC clinicopathological features.
- To evaluate the potential of Dkk1 and Dkk3 as diagnostic and therapeutic targets for ccRCC.
Main Methods:
- Serum Dkk1 and Dkk3 levels were quantified using ELISA in 64 ccRCC patients and 30 healthy controls.
- Dkk1 and Dkk3 mRNA and protein expression were analyzed in tumor and adjacent normal tissues (n=20) using qPCR, Western blot, and immunohistochemistry.
- Correlation analysis was performed between Dkk levels and clinicopathological parameters.
Main Results:
- Mean serum Dkk1 and Dkk3 levels were significantly lower in ccRCC patients compared to controls.
- Lower serum Dkk1 levels correlated with higher tumor-node-metastasis (TNM) stages and tumor grades.
- Tumor tissues exhibited significantly decreased Dkk1 and Dkk3 mRNA and protein expression compared to adjacent normal tissues.
Conclusions:
- Dkk1 and Dkk3 expression is downregulated in ccRCC.
- Serum Dkk1 and Dkk3 levels may serve as potential biomarkers for ccRCC diagnosis.
- Dkk1 and Dkk3 represent promising molecular targets for ccRCC therapeutic strategies.
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