MMP-9和uPA联合检测对胰腺癌预后的价值

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

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。

Objective To explore the value of combined detection with MMP-9 and uPA in the progno-sis of pancreatic carcinoma. Methods By 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. Results The 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＆amp;nbsp;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. Conclusion They 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.