Prognostic value of DKK2 from the Dickkopf family in human breast cancer

Shao,You-Cheng; Nie,Xiao-Cui; Song,Guo-Qing; Wei,Yan; Xia,Pu; Xu,Xiao-Yan

doi:10.3892/ijo.2018.4588

Prognostic value of DKK2 from the Dickkopf family in human breast cancer

Authors:
- You-Cheng Shao
- Xiao-Cui Nie
- Guo-Qing Song
- Yan Wei
- Pu Xia
- Xiao-Yan Xu
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Affiliations: Department of Pathophysiology, College of Basic Medicine Science, China Medical University, Shenyang, Liaoning 110122, P.R. China, Shenyang Maternity and Infant Hospital, Shenyang, Liaoning 110011, P.R. China, Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Cell Biology, College of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: October 9, 2018 https://doi.org/10.3892/ijo.2018.4588
Pages: 2555-2565
Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is one of the most frequently diagnosed types of cancer with a high mortality and malignancy rate in women worldwide. The Dickkopf (DKK) protein family, as a canonical Wnt/β-catenin pathway antagonist, has been implicated in both physiological and pathological processes. This study aimed to comprehensively characterize the prognostic value and elucidate the mechanisms of DKKs in breast cancer and its subtypes. Firstly, DKK mRNA expression and corresponding outcome were analyzed by means of the Gene Expression-Based Outcome for Breast Cancer Online (GOBO) platform based on PAM50 intrinsic breast cancer subtypes. Subsequently, we extracted breast cancer datasets from the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) to validate the expression profile and prognostic values from the GOBO platform. Moreover, a protein-protein network was created and functional enrichment was conducted to explore the underlying mechanisms of action of the DKKs. In addition, we uncovered the genetic and epigenetic alterations of DKK2 in breast cancer. The main finding of this study was the differential roles of DKKs in the PAM50 subtypes of breast cancer analyzed. The overall trend was that a high level of DKK2 was associated with a good survival in breast cancer, although it played an opposite role in the Normal-like subtype. We also found that DKK2 carried out its functions through multiple signaling pathways, not limited to the Wnt/β-catenin cascade in breast cancer. Finally, we used our own data to validate the bioinformatics analysis data for DKK2 by RT-qPCR. Taken together, our findings suggest that DKK2 may be a potential prognostic biomarker for the Normal-like subtype of breast cancer. However, the prognostic role of DKKs in the subtypes of breast cancer still requires validation by larger sample studies in the future.

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