Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer

Liwei Wang, Gary G. Shi, James C. Yao, Weida Gong, Daoyan Wei, Tsung Teh Wu, Jaffer A. Ajani, Suyun Huang, Keping Xie

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background. Angiogenesis is a critical aspect of cancer biology and is subject to regulation by multiple molecular pathways. We evaluated the expression of nitric oxide synthase (NOS) III and its relationship with the angiogenic phenotype and expression of the transcription factor Sp1, as well as their effect on survival in patients with gastric cancer. Methods. The NOS III expression level and tumor microvessel density (MVD) status were determined via immunohistochemistry, using archived tissue specimens from 86 resected gastric cancer cases; these findings were then correlated with Sp1 expression and clinicopathological features. Results. NOS III protein expression was significantly higher in both primary tumors and lymph node metastases than in normal gastric mucosa. In primary tumors, NOS III expression correlated highly with Sp1 expression (P = 0.001) and MVD status (P = 0.001). Patients with strong Sp1 expression were more likely to have strong NOS III expression (15 times) and a high MVD (7 times) than were those with negative Sp1 expression. In univariate survival analyses, strong NOS III expression (P = 0.042), strong Sp1 expression (P = 0.007), and a high MVD (P = 0.036) were associated with worse survival. However, when patients' NOS III and Sp1 expression levels, MVD status, disease stage, completeness of resection, Lauren's classification, and age were entered in a Cox proportional hazards model, only strong NOS III (P = 0.019) and Sp1 expression (P = 0.029) and advanced disease stage (P = 0.006) were independently prognostic of poor survival. Conclusion. Our results indicated that the expression of NOS III, a potential downstream effector of Sp1, may play an important role in tumor angiogenesis and aggressiveness in gastric cancer.

Original languageEnglish (US)
Pages (from-to)18-28
Number of pages11
JournalGastric Cancer
Volume8
Issue number1
DOIs
StatePublished - Feb 2005
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Nitric Oxide Synthase
Stomach Neoplasms
Phenotype
Microvessels
Neoplasms
Survival
Sp1 Transcription Factor
Survival Analysis
Gastric Mucosa
Proportional Hazards Models
Lymph Nodes
Immunohistochemistry
Neoplasm Metastasis

Keywords

  • Angiogenesis
  • Metastasis
  • Prognosis
  • Transcription factor Sp1
  • Tumor

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer. / Wang, Liwei; Shi, Gary G.; Yao, James C.; Gong, Weida; Wei, Daoyan; Wu, Tsung Teh; Ajani, Jaffer A.; Huang, Suyun; Xie, Keping.

In: Gastric Cancer, Vol. 8, No. 1, 02.2005, p. 18-28.

Research output: Contribution to journalArticle

Wang, Liwei ; Shi, Gary G. ; Yao, James C. ; Gong, Weida ; Wei, Daoyan ; Wu, Tsung Teh ; Ajani, Jaffer A. ; Huang, Suyun ; Xie, Keping. / Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer. In: Gastric Cancer. 2005 ; Vol. 8, No. 1. pp. 18-28.
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abstract = "Background. Angiogenesis is a critical aspect of cancer biology and is subject to regulation by multiple molecular pathways. We evaluated the expression of nitric oxide synthase (NOS) III and its relationship with the angiogenic phenotype and expression of the transcription factor Sp1, as well as their effect on survival in patients with gastric cancer. Methods. The NOS III expression level and tumor microvessel density (MVD) status were determined via immunohistochemistry, using archived tissue specimens from 86 resected gastric cancer cases; these findings were then correlated with Sp1 expression and clinicopathological features. Results. NOS III protein expression was significantly higher in both primary tumors and lymph node metastases than in normal gastric mucosa. In primary tumors, NOS III expression correlated highly with Sp1 expression (P = 0.001) and MVD status (P = 0.001). Patients with strong Sp1 expression were more likely to have strong NOS III expression (15 times) and a high MVD (7 times) than were those with negative Sp1 expression. In univariate survival analyses, strong NOS III expression (P = 0.042), strong Sp1 expression (P = 0.007), and a high MVD (P = 0.036) were associated with worse survival. However, when patients' NOS III and Sp1 expression levels, MVD status, disease stage, completeness of resection, Lauren's classification, and age were entered in a Cox proportional hazards model, only strong NOS III (P = 0.019) and Sp1 expression (P = 0.029) and advanced disease stage (P = 0.006) were independently prognostic of poor survival. Conclusion. Our results indicated that the expression of NOS III, a potential downstream effector of Sp1, may play an important role in tumor angiogenesis and aggressiveness in gastric cancer.",
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T1 - Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotype of and predicts poor prognosis in human gastric cancer

AU - Wang, Liwei

AU - Shi, Gary G.

AU - Yao, James C.

AU - Gong, Weida

AU - Wei, Daoyan

AU - Wu, Tsung Teh

AU - Ajani, Jaffer A.

AU - Huang, Suyun

AU - Xie, Keping

PY - 2005/2

Y1 - 2005/2

N2 - Background. Angiogenesis is a critical aspect of cancer biology and is subject to regulation by multiple molecular pathways. We evaluated the expression of nitric oxide synthase (NOS) III and its relationship with the angiogenic phenotype and expression of the transcription factor Sp1, as well as their effect on survival in patients with gastric cancer. Methods. The NOS III expression level and tumor microvessel density (MVD) status were determined via immunohistochemistry, using archived tissue specimens from 86 resected gastric cancer cases; these findings were then correlated with Sp1 expression and clinicopathological features. Results. NOS III protein expression was significantly higher in both primary tumors and lymph node metastases than in normal gastric mucosa. In primary tumors, NOS III expression correlated highly with Sp1 expression (P = 0.001) and MVD status (P = 0.001). Patients with strong Sp1 expression were more likely to have strong NOS III expression (15 times) and a high MVD (7 times) than were those with negative Sp1 expression. In univariate survival analyses, strong NOS III expression (P = 0.042), strong Sp1 expression (P = 0.007), and a high MVD (P = 0.036) were associated with worse survival. However, when patients' NOS III and Sp1 expression levels, MVD status, disease stage, completeness of resection, Lauren's classification, and age were entered in a Cox proportional hazards model, only strong NOS III (P = 0.019) and Sp1 expression (P = 0.029) and advanced disease stage (P = 0.006) were independently prognostic of poor survival. Conclusion. Our results indicated that the expression of NOS III, a potential downstream effector of Sp1, may play an important role in tumor angiogenesis and aggressiveness in gastric cancer.

AB - Background. Angiogenesis is a critical aspect of cancer biology and is subject to regulation by multiple molecular pathways. We evaluated the expression of nitric oxide synthase (NOS) III and its relationship with the angiogenic phenotype and expression of the transcription factor Sp1, as well as their effect on survival in patients with gastric cancer. Methods. The NOS III expression level and tumor microvessel density (MVD) status were determined via immunohistochemistry, using archived tissue specimens from 86 resected gastric cancer cases; these findings were then correlated with Sp1 expression and clinicopathological features. Results. NOS III protein expression was significantly higher in both primary tumors and lymph node metastases than in normal gastric mucosa. In primary tumors, NOS III expression correlated highly with Sp1 expression (P = 0.001) and MVD status (P = 0.001). Patients with strong Sp1 expression were more likely to have strong NOS III expression (15 times) and a high MVD (7 times) than were those with negative Sp1 expression. In univariate survival analyses, strong NOS III expression (P = 0.042), strong Sp1 expression (P = 0.007), and a high MVD (P = 0.036) were associated with worse survival. However, when patients' NOS III and Sp1 expression levels, MVD status, disease stage, completeness of resection, Lauren's classification, and age were entered in a Cox proportional hazards model, only strong NOS III (P = 0.019) and Sp1 expression (P = 0.029) and advanced disease stage (P = 0.006) were independently prognostic of poor survival. Conclusion. Our results indicated that the expression of NOS III, a potential downstream effector of Sp1, may play an important role in tumor angiogenesis and aggressiveness in gastric cancer.

KW - Angiogenesis

KW - Metastasis

KW - Prognosis

KW - Transcription factor Sp1

KW - Tumor

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