The Effect Of Expression Of NEDD4L And HIF-1? In Gastric Cancer On The Prognosis Of Patients

Purpose: To detect the expression of NEDD4 L and HIF-1? in gastric cancer and adjacent normal tissue,and to study the relationship between the expression of NEDD4 L and HIF-1? in gastric cancer and the pathological parameters of gastric cancer,and the relationship between the expression level of NEDD4 L and HIF-1? and the prognosis of gastric cancer patients.Methods: The expression levels of NEDD4 L and HIF-1? in gastric cancer tissues and paired normal tissues were detected by quantitative PCR and Western blot and compared.Then the expression of NEDD4 L and HIF-1? in tissue microarray containing large sample of gastric cancer tissue and normal gastric tissue was detected by immunohistochemical method,and the relationship between expression and clinicopathological parameters and the level of NEDD4 L and HIF-1? expression was analyzed.According to the expression level of NEDD4 L and HIF-1?,divided the patients into four groups,and the relationship between NEDD4 L and hif-1? and prognosis of patients with gastric cancer was analyzed.Results: The expression of NEDD4 L in gastric cancer tissue was lower than that of normal tissue(p<0.05),and the expression of HIF-1? in gastric cancer tissue was higher than that of adjacent normal tissue(p<0.001).The immunohistochemical results of tissue microarray showed that NEDD4 L was positioned in cytoplasm,while HIF-1? was located in nucleus.The positive rate of NEDD4 L in gastric cancer tissue was significantly lower than that in normal tissues(p<0.05),and the positive rate of HIF-1? in gastric carcinoma was significantly higher than that in normal tissues(p=0.001),and NEDD4 L and HIF-1? were negatively correlated(n=124,r= 0.288,p<0.01).The expression of NEDD4 L was distinctly correlated with low differentiation(p=0.039),invasive depth(p=0.025)and clinical TNM staging(p=0.03)of gastric carcinoma,while the expression of HIF-1? protein was associated with tumor size(p=0.049)and infiltration depth(p=0.004).and clinical TNM staging(p=0.014)significantly correlated.There was no significant correlation between the expression level of the two proteins and other pathological parameters,such as sex,age,tumor location,lymph node and metastasis.Kaplan-meier survival analysis showed that tumor size,degree of tissue differentiation,infiltration depth,lymph node metastasis,clinical TNM staging,individual expression of NEDD4 L and HIF-1? were correlated with the prognostic survival of gastric cancer patients.The prognosis of patients with high expression of NEDD4 L and low expression of HIF-1? was better,and the prognosis of high NEDD4 L and low HIF-1? group was worse than that in other groups.Degree of organizational differentiation(HR=2.715,95%CI=1.224-6.023,p<0.05),the expression level of NEDD4L(HR=0.494,95%CI=0.279-0.875,p<0.05),the expression level of HIF-1?(HR=4.922,95 %CI=2.651-9.135,p <0.001),the co-expression levels of NEDD4 L and HIF-1?(HR=0.203,95%CI=0.109-0.377,p<0.001)are independent prognostic factors of gastric cancer.Conclusions:(1).The expression of mRNA and protein in gastric cancer tissue was significantly lower than that of NEDD4 L,while the expression of m RNA and protein in HIF-1? in gastric cancer tissue was significantly higher than that of adjacent normal tissue.(2).The expression levels of NEDD4 L and HIF-1? in gastric cancer tissue were negatively correlated.(3).NEDD4 L is the protective factor of gastric cancer,and HIF-1? is the risk factor of gastric cancer.(4).The prognosis of gastric cancer patients with low NEDD4 L and high HIF-1? expression is poor,and their co-expression status may be the independent prognostic factor of gastric cancer.