Prognostic value of DKK2 from the Dickkopf family in human breast cancer.
Prognostic value of DKK2 from the Dickkopf family in human breast cancer.
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Dickkopf 家族的 DKK2 在人类乳腺癌中的预后价值
DOI：
10.3892/ijo.2018.4588
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发表时间：
2018-12
影响因子：
5.2
通讯作者：
Xu XY
中科院分区：
文献类型：
--
作者：
Shao YC;Nie XC;Song GQ;Wei Y;Xia P;Xu XY
乳腺癌是最常见的癌症类型之一，在全世界女性中具有很高的死亡率和恶性率。Dickkopf(DKK)蛋白家族作为典型的Wnt/β-catenin通路拮抗剂，参与了多种生理和病理过程。本研究旨在全面评价DKKs在乳腺癌及其亚型中的预后价值并阐明其作用机制。首先，基于PAM50固有乳腺癌亚型的乳腺癌基因表达结果在线(GOBO)平台，分析DKK基因的表达和相应的结局。随后，我们从癌症基因组图谱(TCGA)和乳腺癌分子分类国际联合会(METABRIC)中提取乳腺癌数据集，以验证Gobo平台的表达谱和预后价值。此外，还建立了蛋白质-蛋白质网络，并进行了功能丰富，以探索DKK的潜在作用机制。此外，我们还发现了乳腺癌中DKK2基因和表观遗传学的改变。这项研究的主要发现是DKK在所分析的PAM50乳腺癌亚型中的不同作用。总体趋势是，高水平的DKK2与乳腺癌患者的良好生存有关，尽管它在正常亚型中发挥着相反的作用。我们还发现DKK2通过多条信号通路发挥其功能，而不局限于乳腺癌中的Wnt/β-catenin级联反应。最后，我们使用我们自己的数据验证了RT-qPCR对DKK2的生物信息学分析数据。综上所述，我们的发现表明DKK2可能是一个潜在的预后生物标志物，对于正常亚型的乳腺癌来说。然而，DKK在乳腺癌亚型中的预后作用仍需要在未来的更大样本研究中进行验证。
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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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1186/bcr3616
发表时间：
2014-02-14
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Rachner TD;Göbel A;Thiele S;Rauner M;Benad-Mehner P;Hadji P;Bauer T;Muders MH;Baretton GB;Jakob F;Ebert R;Bornhäuser M;Schem C;Hofbauer LC
通讯作者：
Hofbauer LC
DOI：
10.1186/bcr3375
发表时间：
2013-01-15
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Kloten V;Becker B;Winner K;Schrauder MG;Fasching PA;Anzeneder T;Veeck J;Hartmann A;Knüchel R;Dahl E
通讯作者：
Dahl E
影响因子：
2.8
作者：
Hall, Christopher L.;Daignault, Stephanie D.;Shah, Rajal B.;Pienta, Kenneth J.;Keller, Evan T.
通讯作者：
Keller, Evan T.
影响因子：
2.7
作者：
Meng Q;Mongan M;Wang J;Xia Y
通讯作者：
Xia Y