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01-07-2012 | Translational Research and Biomarkers

High Expression of Delta-Like Ligand 4 Predicts Poor Prognosis After Curative Resection for Pancreatic Cancer

Authors: Hai-Tao Chen, MD, Quan-Cai Cai, MD, Jian-Ming Zheng, MD, Xiao-Hua Man, MD, Hui Jiang, MD, Bin Song, MD, Gang Jin, MD, Wei Zhu, MD, Zhao-Shen Li, MD

Published in: Annals of Surgical Oncology | Special Issue 3/2012

Abstract

Background

Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC.

Methods

Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan–Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression.

Results

There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14–4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22–4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42–9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04–10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001).

Conclusions

High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.

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Title: High Expression of Delta-Like Ligand 4 Predicts Poor Prognosis After Curative Resection for Pancreatic Cancer
Authors: Hai-Tao Chen, MD
Quan-Cai Cai, MD
Jian-Ming Zheng, MD
Xiao-Hua Man, MD
Hui Jiang, MD
Bin Song, MD
Gang Jin, MD
Wei Zhu, MD
Zhao-Shen Li, MD
Publication date: 01-07-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-1968-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

High Expression of Delta-Like Ligand 4 Predicts Poor Prognosis After Curative Resection for Pancreatic Cancer

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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