基质金属蛋白酶9、基质金属蛋白酶2、迁移诱导蛋白7和细丝蛋白A在结肠癌中的表达及其预后意义

Expressions of matrix metalloproteinase 9,matrix metalloproteinase 2,migration-inducing protein 7 and filamin A in colon cancer and their prognostic significances

目的探讨基质金属蛋白酶9(MMP-9)、基质金属蛋白酶2(MMP-2)、迁移诱导蛋白7(MIG-7)、细丝蛋白A(FLNa)在结肠癌组织中的表达及其对预后的影响。方法收集2013年1月至2015年12月南京医科大学附属淮安市第一人民医院899例结肠癌患者手术切除的肿瘤标本及其对应的癌旁正常组织。采用酶联免疫吸附试验(ELISA)测定结肠癌组织与癌旁正常组织中MMP-9、MMP-2、MIG-7、FLNa的表达水平,分析其与患者临床病理特征及预后的关系。结果结肠癌组织中MMP-2、MMP-9、MIG-7表达水平分别为(481±69)ng/ml、(262±85)ng/ml、(156±23)ng/ml,均高于癌旁正常组织[分别为(136±33)ng/ml、(191±21)ng/ml、(98±18)ng/ml],差异均有统计学意义(t值分别为41.591、120.224、59.896,均P<0.01);结肠癌组织中FLNa表达水平为(19.5±3.2)ng/ml,低于癌旁正常组织[(65.4±8.3)ng/ml],差异有统计学意义(t=154.902,P<0.05)。结肠癌组织中MMP-9、MMP-2、MIG-7、FLNa表达水平与肿瘤长径、Dukes分期、淋巴结转移、分化程度均有关(均P<0.05)。多因素Cox回归分析结果显示,MMP-9高表达、MMP-2高表达、MIG-7高表达及FLNa低表达均是患者预后不良的独立影响因素(均P<0.05)。Kaplan-Meier生存分析显示,MMP-9、MMP-2、MIG-7低表达患者中位总生存期分别为55个月(95%CI 25-78个月)、56个月(95%CI 26-79个月)、54个月(95%CI 25-78个月),均长于高表达患者;而FLNa高表达患者中位总生存期为58个月(95%CI 27-80个月),长于低表达患者,差异有统计学意义(P<0.05)。结论MMP-9、MMP-2、MIG-7、FLNa与结肠癌的发生、发展密切相关,MMP-9、MMP-2、MIG-7高表达和FLNa低表达均影响结肠癌患者预后,可作为临床预后判断的重要指标。

Objective To investigate the expressions of matrix metalloproteinase 9(MMP-9),matrix metalloproteinase 2(MMP-2),migration-inducing protein 7(MIG-7)and filamin A(FLNa)in colon cancer tissues and their effects on prognosis.Methods The tumor specimens and corresponding adjacent normal tissues of 899 colon cancer patients undergoing surgical resection in the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2013 to December 2015 were collected.The expression levels of MMP-9,MMP-2,MIG-7 and FLNa in colon cancer tissues and adjacent normal tissues were measured by using enzyme-linked immunosorbent assay(ELISA),and the relationship between their expression levels and clinicopathological characteristics as well as prognosis of colon cancer was analyzed.Results The expression levels of MMP-2,MMP-9 and MIG-7 in colon cancer tissues were(481±69)ng/ml,(262±85)ng/ml,(156±23)ng/ml,respectively,which were higher than those in adjacent normal tissues[(136±33)ng/ml,(191±21)ng/ml,(98±18)ng/ml],and the differences were statistically significant(t was 41.591,120.224,59.896,all P<0.01);the expression level of FLNa in colon cancer tissues was(19.5±3.2)ng/ml,which was lower than that in adjacent normal tissues[(65.4±8.3)ng/ml],and the difference was statistically significant(t=154.902,P<0.05).The expression levels of MMP-9,MMP-2,MIG-7 and FLNa in colon cancer tissues were correlated with tumor diameter,Dukes stage,lymph node metastasis and degree of differentiation(all P<0.05).Cox multivariate analysis showed that the high expressions of MMP-9,MMP-2,and MIG-7 and the low expression of FLNa were independent factors affecting the prognosis of patients(all P<0.05).Kaplan-Meier analysis showed that the median overall survival time of patients with low expression of MMP-9,MMP-2 and MIG-7 was 55 months(95%CI 25-78 months),56 months(95%CI 26-79 months)and 54 months(95%CI 25-78 months),respectively,which were longer than those with high expression,while the median overall survival time of patients with high expression of FLNa was 58 months(95%CI 27-80 months),which was longer than those with low expression,and the difference was statistically significant(P<0.05).Conclusions MMP-9,MMP-2,MIG-7 and FLNa are closely related to the occurrence and progression of colon cancer.The high expression levels of MMP-9,MMP-2 and MIG-7 and the low expression level of FLNa have influences on the prognosis of colon cancer patients,and it can be used as important indicators for clinical prognosis judgement.