The Clinical Significance Of ANXA2,MMP-9 And VEGF Expression In Gallbladder Carcinoma And Their Relationship With Angiogenesis

Objective: To explore the expressions of ANXA2,MMP-9 and VEGF in gallbladder carcinoma and their relationship with angiogenesis,and to study their clinical significance in the occurrence and development of gallbladder carcinoma and their influence on prognosis.Methods: The expression and MVD of ANXA2,MMP-9 and VEGF in 65 patients with gallbladder cancer and 30 patients with chronic cholecystitis in the department of General Surgery of the 904 Hospital of the Joint Logistic Support Force of the People’s Liberation Army from January 2012 to December 2019 were determined by immunohistochemistry.The relationship between the expression of ANXA2,MMP-9and VEGF and the clinicopathological features and prognosis of GBC patients was investigated.2 test was used for counting data in this study.T test was used to compare the mean values of the two samples.Kaplan-meier method was used to analyze the postoperative survival of the patients and log-rank test was performed to draw the survival curve.Cox multivariate analysis of the relationship between survival and prognosis of GBC patients;Spearman correlation was used to analyze the correlation between ANXA2,MMP-9,VEGF and MVD values.Results:1.The positive rate of ANXA2 expression in GBC group and chronic cholecystitis group was 36.9%（24/65）and 13.3%（4/30）,respectively,P=0.019.The positive rate of MMP-9 expression was 64.6%（42/65）and 16.7%（5/30）,P=0.000.The positive rate of VEGF expression was 70.8%（46/65）and 23.2%（7/30）,P=0.000.The mean MVD count of 65 patients with gallbladder cancer was 43.58±13.08,and that of 30 patients with chronic cholecystitis was 22.30±3.01,P=0.000.The comparison between the two groups was statistically significant.2.ANXA2,MMP-9,VEGF and MVD in GBC were not significantly related to gender,age,pathological type and tumor location of gallbladder cancer（P>0.05）,but were related to the degree of differentiation,lymph node metastasis and TNM staging of GBC.related（P < 0.05）.3.Univariate analysis showed that the prognosis of GBC patients was related to ANXA2 protein expression,MMP-9 protein expression,VEGF protein expression,MVD count level,gallbladder differentiation,lymph node metastasis,TNM stage and other factors.Multivariate analysis showed that ANXA2 positive expression level（HR:0.418,95.0%CI: 0.209-0.838,P=0.014）,MMP-9 positive expression level（HR:2.718,95.0%CI: 1.342-7.776,P=0.009）,lymph node metastasis（HR:2.328,95.0%CI:1.011-5.361,P=0.047）and TNM stage（HR: 2.330,95.0%CI: 1.089-4.984,P=0.029）were independent risk factors for prognosis of patients with gallbladder cancer.4.Correlation analysis showed that ANXA2 and MMP-9 expression were significantly correlated with VEGF in GBC patients（R = 0.023,R = 0.000）.ANXA2 was significantly correlated with m MP-9 expression in GBC patients（r=0.299,P=0.0.015）.ANXA2 expression was significantly correlated with MVD count（r=0.302,P=0.015）.The expressions of MMP-9 and VEGF were significantly correlated with MVD value（R = 0.491 and 0.431,respectively）.Conclusion:1.The expressions of MMP-9 and VEGF were different in gallbladder cancer tissues and chronic cholecystitis tissues,and both of them were overexpressed in gallbladder cancer tissues,indicating that both of them are closely related to the incidence of gallbladder cancer.There is a positive correlation between MMP9 and VEGF expression in gallbladder cancer,and both of them are positively correlated with MVD value of gallbladder cancer,indicating that both of them can promote angiogenesis of gallbladder cancer.2.In gallbladder cancer tissues,ANXA2 expression is closely related to the differentiation degree of gallbladder cancer,lymph node metastasis,TNM stage and angiogenesis,suggesting that ANXA2 overexpression is an indicator of postoperative survival of gallbladder cancer.3.In gallbladder cancer tissues,MMP-9 expression is closely related to the differentiation degree of gallbladder cancer,lymph node metastasis,TNM stage and angiogenesis,suggesting that MMP-9 overexpression is an indicator of postoperative survival of gallbladder cancer.4.In gallbladder cancer tissues,VEGF expression is closely related to the differentiation degree of gallbladder cancer,lymph node metastasis,TNM stage and angiogenesis,suggesting that VEGF overexpression is an indicator of postoperative survival of gallbladder cancer.5.In gallbladder cancer tissues,ANXA2,MMP-9 and VEGF expression were correlated in a positive manner with MVD value of gallbladder cancer,suggesting that ANXA2 and MMP-9 could promote angiogenesis of gallbladder cancer.