国际肿瘤学杂志 ›› 2015, Vol. 42 ›› Issue (3): 177-181.doi: 10.3760/cma.j.issn.1673422X.2015.03.005

• 论著 • 上一篇    下一篇

MMP-9和uPA联合检测对胰腺癌预后的价值 

李诗杰, 胡军红, 谢永铮, 任学群, 贾富鑫, 刘江伟   

  1. 475000 开封,河南大学淮河医院普外科(李诗杰、胡军红、谢永铮、任学群);郑州大学附属洛阳市中心医院肝胆外科(贾富鑫);兰州军区乌鲁木齐总医院动物实验科(李诗杰、刘江伟)
  • 出版日期:2015-03-08 发布日期:2015-01-29
  • 通讯作者: 刘江伟,Email: ljw273@sohu.com E-mail:ljw273@sohu.com

The value of combined detection with MMP9 and uPA in prognosis of pancreatic carcinoma

 Li-Shi-Jie, HU  Jun-Hong, XIE  Yong-Zheng, REN  Xue-Qun, JIA  Fu-Xin, LIU  Jiang-Wei   

  1. Department of General Surgery, Henan University Huaihe Hospital, Kaifeng 475000, China
  • Online:2015-03-08 Published:2015-01-29
  • Contact: Liu Jiangwei E-mail:ljw273@sohu.com

摘要: 目的探讨基质金属蛋白酶9(MMP9)、尿激酶型纤溶酶原激活剂(uPA)二者联合检测在胰腺癌预后判断中的价值。方法采用免疫组织化学二步法检测63例手术切除的原发性胰腺癌组织中MMP9、uPA的表达,分析二者对预后的价值。结果MMP9与uPA的表达呈正相关(r=0.573,P=0.000),MMP9和uPA表达与胰腺癌的分化程度(r=-0.271,P=0.032;r=-0.333,P=0.008)、TNM分期(r=-0.449,P=0.000;r=-0.430,P=0.000)及淋巴结转移(r=0.329,P=0.009;r=0.400,P=0.001)相关,而MMP9与肿瘤大小(r=-0.297,P=0.018,)及远处转移(r=0.320,P=0.011)也存在明显相关性。单因素预后分析结果显示,肿瘤大小(χ2=8.766,P=0.012)、分化程度(χ2=29.050,P=0.000)、临床分期(χ2=24.940,P=0.000)、远处转移(χ2=12.846,P=0.000)、淋巴结转移(χ2=15.457,P=0.000)、MMP9(χ2=32.700,P=0.000)及uPA(χ2=41.495,P=0.000)与预后密切相关。KaplanMeier法生存分析表明,MMP9阳性表达及阴性表达患者1年累计生存率(χ2=32.700,P=0.000)与uPA阳性表达及阴性表达患者1年累计生存率差异均有统计学意义(χ2=41.495,P=0.000);MMP9阴性并uPA阴性组患者1年累计生存率(100%)明显高于其他组,差异有统计学意义(χ2= 54.892,P=0.000)。多因素分析结果表明,分化程度(RR=2.315,P=0.004)、临床分期(RR=1.694,P=0.002)、MMP9(RR=0.165,P=0.000)及uPA过表达(RR=0.244,P=0.007)是胰腺癌预后相关的独立影响因子。结论胰腺癌侵袭转移过程中MMP9和uPA蛋白之间存在某种协同关系,uPA可能通过激活MMP9加强胶原及弹性蛋白等的降解而促进胰腺癌细胞侵袭和转移,不利于胰腺癌预后。MMP9 和uPA的联合表达模式更准确反映胰腺癌的预后,可以作为分化程度、临床分期判断胰腺癌预后的有益补充。

关键词: 胰腺肿瘤, 预后, 基质金属蛋白酶9, 尿激酶型纤溶酶原激活物

Abstract: ObjectiveTo explore the value of combined detection with MMP9 and uPA in the prognosis of pancreatic carcinoma. MethodsBy immunohistochemistry PV methods,the expression of MMP9 and uPA was respectively studied in 63 surgical specimens of primary pancreatic carcinoma and the survival time of patients with pancreatic carcinoma was analysed. ResultsThe expressions of MMP9 and uPA  were positively related (r=0.573,P=0.000). The expression of MMP9 and uPA significantly correlated with differentiation(r=-0.271,P=0.032;r=-0.333,P=0.008), TNM stages(r=-0.449,P=0.000;r=-0.430,P=0.000)and lymph node metastasis(r=0.329,P=0.009;r=0.400,P=0.001), separately. The expression of MMP9 had also a significant correlation with tumer size(r=-0.297,P=0.018)and distant metastasis(r=0.320,P=0.011).Univariate analysis identified that tumor size(χ2=8.766,P=0.012),differentiation(χ2=29.050,P=0.000),clinical stage(χ2=24.940,P=0.000),distant metastasis(χ2=12.846,P=0.000),lymph node metastasis(χ2=15.457,P=0.000),MMP9(χ2=32.700,P=0.000)and uPA(χ2=41.495,P=0.000)were significantly associated with prognosis. KaplanMeier survival analysis showed that 1year survival rate of patients with MMP9 (-),uPA (-)were significantly longer than that of the patients with MMP9 (+),uPA (+),respectively(χ2=32.700,P=0.000;χ2=41.495,P=0.000);1year survival rate of  patients with MMP9 (-)/uPA(-)was significantly longer than the others(Logrank test,χ2= 54.892, P=0.000).COX regression revealed that differentiation (RR=2.315,P=0.004),clinical stage(RR=1.694,P=0.002),MMP9(RR=0.165,P=0.000) and uPA(RR=0.244,P=0.007)was independent prognostic factors in pancreatic carcinoma. ConclusionThey may have a synergistic function in the the process of growth and invasion in pancreatic cancer between MMP9 and uPA, and the posssible mechanism is that uPA activate degradation of MMP9, which is not favorable to prognosis.Combined analysis of MMP9 and uPA may lead to a more reliable prognostic estimation,as the beneficial supplement of the differentiation, and clinical stage to judge the prognosis of pancreatic cancer.

Key words: Pancreatic neoplasms, Prognosis, Matrix metalloproteinase 9, Urinary plasminogen actirator