Clinical implications of DLL4 expression in gastric cancer

Journal of Experimental & Clinical Cancer Research

Shoji Natsugoe¹  Shinichi Ueno¹  Tetsuro Owaki¹  Akihiro Nakajo¹  Yuka Nishizono¹  Yuko Kijima¹  Yoshiaki Kita¹  Tetsuro Setoyama¹  Yasuto Uchikado¹  Hiroshi Kurahara¹  Hiroshi Okumura¹  Yoshikazu Uenosono¹  Takaaki Arigami¹  Sumiya Ishigami¹ 

[1] Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University School of Medicine, Sakuragaoka, Kagoshima 890-8520, Japan

关键词: Peritumoral stroma;    Gastric cancer;    Lymph node metastases;    Lymphatic invasion;    Delta-like ligand 4;   

Others  :  824853
DOI  :  10.1186/1756-9966-32-46

 received in 2013-03-08, accepted in 2013-07-16,  发布年份 2013

【 摘 要 】

Background

Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor neovascular development and angiogenesis during tumor growth. The clinical significance of DLL4 expression in gastric cancer has not been clarified.

Methods

Gastric cancer cell lines and 180 gastric cancer patients were enrolled. DLL4 expression in gastric cancer cells and stroma was identified and evaluated immunohistochemically. The association between DLL4 and clinicopathological factors was also assessed.

Results

DLL4 expression was identified in the cellular membrane and cytoplasm of gastric cancer cells by immunoblotting and immunohistochemical staining. DLL4 positivity in cancer cells and stroma was found in 88 (48%) and 41 (22%) of the 180 gastric cancer patients respectively. Both cancer and stromal DLL4 expression significantly correlated with more advanced tumor depth, nodal involvement, and lymphatic and venous invasion. A strongly positive association between cancerous and stromal DLL4 expression was identified (p < 0.01). Both cancerous and stromal DLL4 expression were prognostic markers in gastric cancer as determined by univariate analysis.

Conclusions

Cancerous and stromal DLL4 expression was found in 48% and 22% in gastric cancer, and significantly affected postoperative clinical outcomes. Cancerous and stromal DLL4 expression may be an effective target of anti-DLL4 treatment in gastric cancer.

【 授权许可】

   
2013 Ishigami et al.; licensee BioMed Central Ltd.

【 图 表 】

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