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Over-expression of both VEGF-C and Twist predicts poor prognosis in human breast cancer

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Abstract

Background

Angiogenesis is an indispensable step in the growth and invasiveness of breast cancers involving a series of exquisite molecular steps. Pro-angiogenic factors, including vascular endothelial growth factor (VEGF), have been recognized as pivotal therapeutic targets in the treatment of breast cancer. More recently, a highly conserved transcription factor Twist has been reported to be involved in tumor angiogenesis and metastasis.

Methods

The expression of VEGF-C and Twist was immunohistochemically determined in tissue samples of primary tumors from 408 patients undergoing curative surgical resection for breast cancer. The correlations of VEGF-C and Twist expressions with clinicopathologic parameters as well as survival outcomes were evaluated.

Results

Of the 408 patients evaluated, approximately 70% had high expression of VEGF-C which was significantly associated with advanced tumor stages (P = 0.019). Similarly, VEGF-C expression was associated with the proliferation index Ki67, N3 lymph node metastasis, and D2-40-positive lymphatic vessel invasion (LVI) in a univariate analysis. Furthermore, patients with high expressions of VEGF-C and Twist (V + T+) had significantly increased lymph node metastasis, higher clinical stage, and worse disease-free survival, DFS (P = 0.001) and overall survival, OS (P = 0.011).

Conclusions

Our results suggested that co-expression of VEGF-C and Twist was associated with larger tumor size, higher numbers of lymph node involvement, D2-40-positive LVI, higher risk of distant metastasis, and worse DFS or OS in breast cancer patients.

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Funding

This study was funded by Natural Science Foundation Committee (No.81602345), Shantou science and technology program, China (No.123,2015), Science and Technology Planning Project of Guangdong Province, China (2016A020215145), Medical Scientific Research Foundation of Guangdong Province, China (A2016589) and Start-Up Funds from Xiamen University.

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Author notes

  1. Y.-Q. Zhang and W.-L. Chen contributed equally to this work.

Authors and Affiliations

  1. The Breast Center, Cancer Hospital of Shantou University Medical College, 7 Rao ping Road, Shantou, China

    Y.-Q. Zhang, J.-D. Wu, C.-P. Guo, H.-C. Zeng & W.-H. Huang

  2. Chang Jiang Scholar’s Laboratory of Shantou University Medical College, 22 Xin ling Road, Shantou, China

    Y.-Q. Zhang, D. Zeng, Y.-K. Liang, S.-S. Hao, R.-H. Li & G.-J. Zhang

  3. Department of Head Neck and Breast Surgery, Yue Bei People’s Hospital, 133 Huimin South Road, Shao Guan, China

    W.-L. Chen

  4. Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, 7 Rao ping Road, Shantou, China

    F. Zhang

  5. Department of Pathology, Cancer Hospital of Shantou University Medical College, 7 Rao ping Road, Shantou, China

    X.-L. Wei & L.-Y. Zhang

  6. Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Y.-K. Liang

  7. The Cancer Center and Breast-Thyroid-Surgery, Xiang’ an Hospital of Xiamen University, Xiamen, China

    W.-H. Huang & G.-J. Zhang

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  1. Y.-Q. Zhang
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Correspondence to W.-H. Huang or G.-J. Zhang.

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The authors have declared that no competing interests exist.

Ethical approval

The work was conducted in accordance with the Declaration of Helsinki. Written informed consents were obtained from all patients, in particular, for the use of human tissues, and the study protocol was approved by the medical ethics committee of the Cancer Hospital of Shantou University Medical College.

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Cite this article

Zhang, YQ., Chen, WL., Zhang, F. et al. Over-expression of both VEGF-C and Twist predicts poor prognosis in human breast cancer. Clin Transl Oncol 21, 1250–1259 (2019). https://doi.org/10.1007/s12094-019-02051-9

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  • DOI: https://doi.org/10.1007/s12094-019-02051-9

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