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

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 brea...

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Published in:	Clinical & translational oncology 2019-09, Vol.21 (9), p.1250-1259
Main Authors:	Zhang, Y.-Q., Chen, W.-L., Zhang, F., Wei, X.-L., Zeng, D., Liang, Y.-K., Wu, J.-D., Zhang, L.-Y., Guo, C.-P., Zeng, H.-C., Hao, S.-S., Li, R.-H., Huang, W.-H., Zhang, G.-J.
Format:	Article
Language:	eng
Subjects:	Biomarkers, Tumor - metabolism Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - surgery Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - pathology Carcinoma, Ductal, Breast - surgery Female Follow-Up Studies Gene Expression Regulation, Neoplastic Humans Medicine Medicine & Public Health Middle Aged Nuclear Proteins - metabolism Oncology Prognosis Research Article Survival Rate Twist-Related Protein 1 - metabolism Vascular Endothelial Growth Factor C - metabolism
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Summary:	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.
ISSN:	1699-048X 1699-3055