基质金属蛋白酶2、整合素⁃金属蛋白酶17及上皮性钙粘附蛋白E在结直肠癌癌组织中的表达及临床意义

Expression and clinical significance of MMP⁃2,ADAM17 and E⁃cadherin in colorectal cancer tissues

目的探讨基质金属蛋白酶2(MMP⁃2)、整合素⁃金属蛋白酶17(ADAM17)及上皮性钙黏附蛋白E(E⁃cadherin)在结直肠癌癌组织中的表达及临床意义。方法采用免疫组化及Western blot方法检测210例结直肠癌组织标本及癌旁组织中MMP⁃2、ADAM17及E⁃cadherin的表达水平,分析MMP⁃2、ADAM17及E⁃cadherin表达水平及其与临床病理特征的关系,探讨三者表达水平与患者预后关系,并分析其相关性。结果MMP⁃2在结直肠癌组织中的阳性表达率72.38%显著高于癌旁组织的19.52%,差异有统计学意义(P<0.05);ADAM17阳性表达率为78.10%(164/210),显著高于癌旁组织的5.24%,差异有统计学意义(P<0.05);E⁃cadherin在癌组织中的阳性表达率为41.90%,显著低于癌旁组织的96.67%,差异有统计学意义(P<0.05);Western blot结果显示,癌组织中的MMP⁃2、ADAM17蛋白表达水平显著高于癌旁组织,E⁃cadherin蛋白表达水平显著低于癌旁组织,差异有统计学意义(P<0.05);MMP⁃2、ADAM17及E⁃cadherin阳性表达与TNM分期、分化程度、淋巴结转移、肝转移有关(P<0.05),与患者性别分布、年龄、肿瘤大小、发生部位无关(P>0.05);MMP⁃2阳性组中位生存期22个月(95%CI:20.87~23.58),5年生存率53.42%,MMP⁃2阴性组中位生存期31个月(95%CI:28.95~33.45),5年生存率69.18%,两组生存情况比较差异有统计学意义(Log⁃rankχ2=4.98,P<0.05);ADAM17阳性组中位生存期21个月(95%CI:19.93~22.86),5年生存率50.77%,ADAM17阴性组中位生存期33个月(95%CI:30.48~36.40),5年生存率65.52%,两组生存情况比较差异有统计学意义(Log⁃rankχ2=7.28,P<0.05);E⁃cadherin阳性组中位生存期30个月(95%CI:27.88~31.32),5年生存率47.92%,E⁃cadherin阴性组中位生存期16个月(95%CI:14.60~17.89),5年生存率26.09%,两组生存情况差异比较有统计学意义(Log⁃rankχ2=44.23,P<0.05);Spearman相关性结果显示,MMP⁃2表达与ADAM17表达呈正相关(P<0.05),MMP⁃2表达与E⁃cadherin表达呈负相关(P<0.05),ADAM17表达与E⁃cadherin表达呈负相关(P<0.05)。结论MMP⁃2、ADAM17在结直肠癌组织中的表达水平显著高于癌旁组织,E⁃cadherin在结直肠癌组织中的表达水平显著低于癌旁组织,其表达与患者临床分期、分化程度、淋巴结转移、肝转移有关,三种蛋白表达水平与患者预后密切相关,且结直肠癌组织中MMP⁃2表达与ADAM17表达呈正相关,E⁃cadherin表达与MMP⁃2、ADAM17表达呈负相关,检测三种蛋白表达水平可作为诊断结直肠癌以及评估预后的标志。

Objective To explore the expression and clinical significance of matrix metalloproteinase⁃2(MMP⁃2),a disinterring and metalloproteinase 17(ADAM17)and epithelial cadherin E(E⁃cadherin)in colorectal cancer tissues.Methods The expression levels of MMP⁃2,ADAM17 and E⁃cadherin in cancer tissues specimens and adjacent tissues of 210 cases of colorectal cancer were detected by immunohistochemistry and Western blot.The expression levels of MMP⁃2,ADAM17 and E⁃cadherin and their relationship with clinicopathological features were analyzed,and the relationship between the three expression levels and prognosis was analyzed,and its corre⁃lation was analyzed.Results The positive expression rate of MMP⁃2 in colorectal cancer tissues was significantly higher than that in adjacent tissues(72.38%vs.19.52%,P<0.05).The positive expression rate of ADAM17 was significantly higher than that in adjacent tissues[78.10%(164/210)vs.5.24%,P<0.05)].The positive expression rate of E⁃cadherin in cancer tissues was significantly lower than that in adjacent tissues(41.90%vs.96.67%,P<0.05).Western blot results showed that the protein expression levels of MMP⁃2 and ADAM17 in cancer tissues were significantly higher than those in adjacent tissues while the protein expression level of E⁃cadherin was signifi⁃cantly lower than that in adjacent tissues(P<0.05).The positive expressions of MMP⁃2,ADAM17 and E⁃cadherin were associated with TNM stage,differentiation degree,lymph node metastasis and liver metastasis(P<0.05),and were not related to gender distribution,age,tumor size and location(P>0.05).The median survival time was 22 months(95%CI:20.87~23.58)and the 5⁃year survival rate was 53.42%in MMP⁃2 positive group,and median survival time was 31 months(95%CI:28.95~33.45)and the 5⁃year survival rate was 69.18%in MMP⁃2 negative group,and there was a statistical difference in the survival between the two groups(Log⁃rankχ2=4.98,P<0.05).The median survival time was 21 months(95%CI:19.93~22.86)and the 5⁃year survival rate was 50.77%in ADAM17 positive group,and the median survival time was 33 months(95%CI:30.48~36.40)and the 5⁃year survival rate was 65.52%in ADAM17 negative group,and there was a statistically significant difference in the survival between the two groups(Log⁃rankχ2=7.28,P<0.05).The median survival time was 30 months(95%CI:27.88~31.32)and the 5⁃year survival rate was 47.92%in E⁃cadherin positive group,and the median survival time was 16 months(95%CI:14.60~17.89)and the 5⁃year survival rate was 26.09%in E⁃cadherin negative group,and there was a statistically significant difference in the survival between the two groups(Log⁃rankχ2=44.23,P<0.05).Spearman correlation showed that MMP⁃2 expression was positively correlated with ADAM17 expression(P<0.05),and MMP⁃2 expression was significantly negatively correlated with E⁃cadherin expression(P<0.05),and ADAM17 expression was significantly negatively correlated with E⁃cadherin expression(P<0.05).Conclusion The expression levels of MMP⁃2 and ADAM17 in colorectal cancer tissues are significantly higher than those in adjacent tissues while the expression level of E⁃cadherin in colorectal cancer tissues is significantly lower than that in adjacent tissues.Their expressions are related to clinical stage,differentiation degree,lymph node metastasis and liver metastasis.The expression levels of three proteins are closely related to the prognosis of patients,and the expression of MMP⁃2 is positively correlated with the expression of ADAM17 in colorectal cancer tissues.E⁃cadherin expression is significantly negatively correlated with the expressions of MMP⁃2 and ADAM17.The detec⁃tion of three protein expression levels can be used as a marker for the diagnosis of colorectal cancer and assessment of prognosis.