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Elevated DLL4 expression is correlated with VEGF and predicts poor prognosis of nasopharyngeal carcinoma.
MedLine Citation:
PMID:  23275120     Owner:  NLM     Status:  Publisher    
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.
Jia-Xing Zhang; Man-Bo Cai; Xiao-Pai Wang; Li-Ping Duan; Qiong Shao; Zhu-Ting Tong; Ding-Zhun Liao; Yang-Yang Li; Ma-Yan Huang; Yi-Xin Zeng; Jian-Yong Shao
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-30
Journal Detail:
Title:  Medical oncology (Northwood, London, England)     Volume:  30     ISSN:  1559-131X     ISO Abbreviation:  Med. Oncol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9435512     Medline TA:  Med Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  390     Citation Subset:  -    
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
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