Clinical Significance Of HIF-1α And VEGF Expression In Pancreatic Cancer

ObjectivePancreatic cancer is one of the frequent occurred malignant tumors. Although it is cured by operation-based comprehensive therapies, the one-year survival rate following curative resection is less than 12 percent, and the five-year survival rate is about 1 precent to 4 precent in recent years. Because most pancreatic cancers are categorized as developing stage when they are diagnosed in clinic, the figure remains high. Therefore, studing its happening, invasion and metastasis are most valuable as well as diagnosis and treatment in early stage.Hypoxia-inducible factor 1 (HIF-1) is an important transcription factor in mammals, which is a key factor in the hypoxia response of tumor. HIF-1α is special regulative subunits: hypoxia can increase the level of HIF-1α protein, then HIF-1α subunits bind the hypoxia responseive elements (HREs) of target genes with the β subunits and co-active factors (such as CBP, P300), enhances the mRNA level of target genes. The amino acids 401-603 of HIF-1α protein are the oxygen-dependent degradation domain (ODD). MF-1α protein are polyubiquitinated by composing the ubiquitin-ligase complex through binding the protein VHL (von hippel lindau), then the HIF-1α subunits are degraded rapid by protease (<5min). The low O₂ concertration can inhibit the degradation of HIF-1 and enhance the HIF-1α protein. VEGF is one of the important target genes of HIF-1. Hypoxia can increase the level and stability of VEGF mRNA. HIF-1 can target the HRE (5'-TACGTGGC-3') to enhance the transcription of VEGF gene. In addition, the RNA binding protein can bind the A,U richly sequence in 3' end of VEGF mRNA, to stop the degradation of mRNA.In this study, the expressions of HIF-1α and VEGF in pancreastic cancer were evaluated, and may be promote the therapeutic genic targets of pancreatic cancer.Methods1. Western blot was used to evaluate the levels of HIF-1α and VEGF in pancreatic cancer tissues and pancreatic para-cancer tissues.2. The reationship and clinical significance of HIF-1α and VEGF expression in pancreatic cancer was analysised with the clinical data.Results1. Expressions of HIF-1α and VEGF in pancreatic cancer tissue were significantly higher than that in para-cancer tissue, and the expression of HIF-1α was positively correlated with VEGF.2. The levels of HIF-1α and VEGF were closely related with the size of tumor, the lymphnodus metastasis and TNM stage.ConclusionsOver-expressions of HIF-1α and VEGF were found in pancreatic cancer. HIF-1α and VEGF may play important roles in the carcinogenesis and aggression in pancreatic cancer. HIF-1α may be a useful marker for evaluating prognosis in pancreatic cance.