基质金属蛋白酶2、血管内皮生长因子在胆囊癌中的表达及与患者预后的关系

Expression of matrix metalloproteinase 2 and vascular endothelial growth factor in gallbladder carcinoma and its relationship with patient prognosis

目的探讨基质金属蛋白酶2(MMP2)、血管内皮生长因子(VEGF)在胆囊癌中的表达及与患者预后的关系。方法取96例胆囊癌患者的胆囊癌组织和96例胆囊息肉患者的胆囊息肉组织,酶联免疫吸附测定检测胆囊癌和胆囊息肉患者MMP2、VEGF、VEGFC受体VEGFR3(Flt4)水平;免疫组化法检测胆囊癌组织和胆囊息肉组织中MMP2、VEGF蛋白的表达情况,分析MMP2、VEGF蛋白表达情况与胆囊癌患者临床特征及随访3年生存情况的关系。结果术后1周,两组患者血清MMP2、VEGF、Flt4水平均明显低于本组术前1天,且观察组患者血清MMP2、VEGF、Flt4水平均明显高于对照组患者,差异均有统计学意义(P﹤0.01)。胆囊癌组织中MMP2蛋白的阳性表达率为64.58%,明显高于胆囊息肉组织的35.42%,VEGF蛋白的阳性表达率为42.71%,明显高于胆囊息肉组织的0%,差异均有统计学意义(P﹤0.01)。随着浸润深度的加深,胆囊癌患者胆囊癌组织中MMP2、VEGF蛋白阳性表达率逐渐升高,TNM分期为Ⅲ-Ⅳ期、有淋巴结转移、分化程度为低分化胆囊癌患者胆囊癌组织中MMP2、VEGF蛋白阳性表达率均高于TNM分期Ⅰ-Ⅱ期、无淋巴结转移和分化程度为中高分化的患者,差异均有统计学意义(P﹤0.05)。随访3年,MMP2阳性表达胆囊癌患者3年生存率为64.52%,低于阴性表达患者的88.24%,VEGF阳性表达胆囊癌患者3年生存率为51.22%,低于VEGF阴性表达患者的96.36%,差异均有统计学意义(P﹤0.05)。结论胆囊癌患者血清MMP2、VEGF水平较高,且MMP2、VEGF蛋白的表达情况对胆囊癌患者的预后有一定的预测价值,其阳性表达患者预后较差。

Objective To explore the expression of matrix metalloproteinase 2(MMP2)and vascular endothelial growth factor(VEGF)in gallbladder carcinoma and its relationship with the prognosis of patients.Method The cancer tissue from 96 patients with gallbladder cancer and the normal tissue from 96 patients with gallbladder polyps were taken.Enzyme-linked immunosorbent assay was employed to measure serum MMP2,VEGF,and VEGFC receptor VEGFR3(Flt4)levels in patients with gallbladder cancer and gallbladder polyps.Immunohistochemical assay was used to detect the expression of MMP2 and VEGF protein in gallbladder cancer tissue and gallbladder polyp tissue.The expression of the indicators and their relationship with the clinical features of gallbladder cancer patients and the overall survival during a 3-year follow-up were analyzed.Result One week after the operation,the serum levels of MMP2,VEGF,and Flt4 in the two groups were significantly lower than those in the group one day before surgery,and the levels of serum MMP2,VEGF,and Flt4 in the observation group were significantly higher than those in the control group,the differences were statistically significant(P<0.01).The positive rate of MMP2 protein in gallbladder cancer tissue was 64.58%,which was significantly higher than 35.42%in gallbladder polyp tissue,the positive rate of VEGF protein was 42.71%,which was also significantly higher than 0%in gallbladder polyp tissue,and the differences were statistically significant(P<0.01).With the increase of the depth of invasion,the positive rate of MMP2,VEGF protein in the cancer tissues of patients with gallbladder cancer gradually increased.The positive rates of MMP2,VEGF protein in the gallbladder cancer patients with TNM stageⅢ-Ⅳ,lymph node metastasis,and poorly differentiated gallbladder carcinoma were higher than those whose TNM stage wasⅠ-Ⅱ,without lymph node metastasis and medium to high differentiated grade,and the differences were statistically significant(P<0.05).After 3-year of follow-up,the 3-year overall survival of gallbladder cancer patients with MMP2 positive expression was 64.52%,lower than 88.24%of patients with negative expression,the 3-year overall survival of gallbladder cancer patients with VEGF positive expression was 51.22%,significantly lower than the 96.36%of patients with negative VEGF expression,and the differences were statistically significant(P<0.05).Conclusion The serum levels of MMP2 and VEGF are up-regulated in patients with gallbladder cancer.The expression of MMP2 and VEGF protein has a particular predictive value for the prognosis of patients with gallbladder cancer,which means the prognosis of patients with positive expression is poor.