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Elevated DLL4 expression is correlated with VEGF and predicts poor prognosis of nasopharyngeal carcinoma

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Abstract

Delta-like ligand 4 (DLL4), one of the transmembranous Notch ligands, is upregulated at the site of tumor growth, particularly during tumor angiogenesis. Expression pattern of DLL4 in nasopharyngeal carcinoma (NPC) and the clinical and prognostic significance remain unclear. In this study, immunohistochemical analysis (IHC) was used to examine the protein level of DLL4 in NPC tissues from two independent cohorts. In the testing cohort (311 cases), we applied the X-tile program software able to assess the optimal cutoff points for biomarkers in order to accurately classify patients according to clinical outcome. In the validation cohort (113 cases), the cutoff score derived from X-title analysis was investigated to determine the association of DLL4 expression with disease-specific survival (DFS). Our results showed that high expression of DLL4 was observed in 134 of 313 (42.8 %) in the testing cohort and 58 of 113 (43.6 %) in the validation cohort. High expression of DLL4 independently predicted poorer disease-specific survival, as evidenced by univariate and multivariate analysis (P < 0.05). Moreover, DLL4 expression was significantly elevated in distant NPC metastases relative to primary NPC tumors (P = 0.001). Importantly, we found a significant positive relationship between DLL4 and vascular endothelial growth factor (VEGF) (P < 0.001). Patients with dual elevated DLL4 and VEGF expression displayed a significant overall survival disadvantage compared to those with dual low expression (P < 0.05). These findings provide evidence that high expression of DLL4 serves as an independent predictor of poor prognosis in NPC patients.

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Acknowledgments

This study was supported in part by National High Technology Research and Development Program of China (863 Program) (2012AA02A501); the China State Key Basic Research Project (2011CB504805).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

    Jia-Xing Zhang, Yi-Xin Zeng & Jian-Yong Shao

  2. Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

    Jia-Xing Zhang, Xiao-Pai Wang, Qiong Shao, Yang-Yang Li & Jian-Yong Shao

  3. Department of Experiment Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

    Man-Bo Cai & Yi-Xin Zeng

  4. Institute of Scientific and Technical Information of China (ISTIC), 100038, Beijing, China

    Li-Ping Duan

  5. Department of Radiotherapy, The First Affiliated Hospital, An Hui Medical University, Hefei, China

    Zhu-Ting Tong

  6. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

    Ding-Zhun Liao & Ma-Yan Huang

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  1. Jia-Xing Zhang
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  2. Man-Bo Cai
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Correspondence to Jian-Yong Shao.

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Jia-Xing Zhang, Man-Bo Cai and Xiao-Pai Wang: These authors made equal contributions and are joint first authors.

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Zhang, JX., Cai, MB., Wang, XP. et al. Elevated DLL4 expression is correlated with VEGF and predicts poor prognosis of nasopharyngeal carcinoma. Med Oncol 30, 390 (2013). https://doi.org/10.1007/s12032-012-0390-x

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  • DOI: https://doi.org/10.1007/s12032-012-0390-x

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