Clinical implications of DLL4 expression in gastric cancer

Sumiya Ishigami, Takaaki Arigami, Yoshikazu Uenosono, Hiroshi Okumura, Hiroshi Kurahara, Yasuto Uchikado, Tetsuro Setoyama, Yoshiaki Kita, Yuko Kijima, Yuka Nishizono, Akihiro Nakajo, Tetsuro Owaki, Shinichi Ueno, Shoji Natsugoe

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number46
JournalJournal of Experimental and Clinical Cancer Research
Volume32
Issue number1
DOIs
Publication statusPublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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