BACKGROUND: Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma (PDAC). We evaluated whether the immunohistochemistry for hypoxia inducible factor-1α (HIF-1α) was correlated with hepatic metastases in PDAC. METHODS: We examined the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A), thymidine phosphorylase (TP) and basic fibroblast growth factor (bFGF) in a total of 100 paraffin-embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathological correlations. We determined microvessel count (MVC) and apoptotic index (AI), and assessed their correlations with hepatic metastases. Student's t-test, the Mann-Whitney U-test, and Spearman correlation coefficients were used to validate the model, and regression analysis was used to test the model. RESULTS: Hypoxia inducible factor-1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI. HIF-1α expression (P = 0.0087) and angiogenic factors (P = 0.0079) were significantly associated with not only the microvessel status (P = 0.022) but also the high incidence of hepatic metastasis (P = 0.02), resulting in the worse survival of PDAC patients (P < 0.05). CONCLUSIONS: Hypoxia inducible factor-1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDAC patients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.
BACKGROUND:Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma (PDAC). We evaluated whether the immunohistochemistry for hypoxia inducible factor-1α (HIF-1α) was correlated with hepatic metastases in PDAC. METHODS: We examined the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A), thymidine phosphorylase (TP) and basic fibroblast growth factor (bFGF) in a total of 100 paraffin-embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathological correlations. We determined microvessel count (MVC) and apoptotic index (AI), and assessed their correlations with hepatic metastases. Student's t-test, the Mann-Whitney U-test, and Spearman correlation coefficients were used to validate the model, and regression analysis was used to test the model. RESULTS:Hypoxia inducible factor-1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI. HIF-1α expression (P = 0.0087) and angiogenic factors (P = 0.0079) were significantly associated with not only the microvessel status (P = 0.022) but also the high incidence of hepatic metastasis (P = 0.02), resulting in the worse survival of PDACpatients (P < 0.05). CONCLUSIONS:Hypoxia inducible factor-1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDACpatients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.
Authors: Shingo Matsumoto; Shun Kishimoto; Keita Saito; Yoichi Takakusagi; Jeeva P Munasinghe; Nallathamby Devasahayam; Charles P Hart; Robert J Gillies; James B Mitchell; Murali C Krishna Journal: Cancer Res Date: 2018-05-23 Impact factor: 12.701
Authors: Justin G Wilkes; Brianne R O'Leary; Juan Du; Adrienne R Klinger; Zita A Sibenaller; Claire M Doskey; Katherine N Gibson-Corley; Matthew S Alexander; Susan Tsai; Garry R Buettner; Joseph J Cullen Journal: Clin Exp Metastasis Date: 2018-02-02 Impact factor: 5.150
Authors: Christopher Montemagno; Shamir Cassim; Nicolas De Leiris; Jérôme Durivault; Marc Faraggi; Gilles Pagès Journal: Int J Mol Sci Date: 2021-06-15 Impact factor: 5.923