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目的研究尿激酶型纤溶酶原激活系统uPA,uPAR,PAI-1蛋白及血管内皮生长因子(VEGF)在直肠癌组织中的表达及其与直肠癌癌生物学行为的关系。方法2005年1月至2006年1月,采用免疫组化S-P法检测67例直肠癌及癌旁组织中uPA,uPAR,PAI-1及VEGF蛋白表达情况,同时对临床病理学资料进行回顾性分析。结果癌和癌周比较uPA,uPAR,PAI-1及VEGF蛋白阳性表达率明显升高(P<0.01),阳性产物主要分布在癌细胞胞质。侵及浆膜组阳性率明显高于未及浆膜组(P=0.000,0.014,0.016,0.000)。uPA,uPAR蛋白在淋巴结转移组中的阳性率明显高于无淋巴结转移组(P=0.002,0.008)。PAI-1蛋白在低分化组中的阳性率明显低于中分化和高分化组(P<0.05)。uPA,uPAR及VEGF蛋白阳性率在直肠癌组织不同分化程度间差异无显著性。在直肠癌组织中uPA,uPAR蛋白的表达呈显著正相关(r=0.653,P<0.001)。在uPA,uPAR蛋白同时阳性的41例病例中,有28例发生淋巴结转移,与阴性组(4/15)相比,转移发生率明显增高(P<0.01)。直肠癌组织中uPA蛋白表达与VEGF表达显著正相关(r=0.300,P<0.05)。PAI-1蛋白表达与VEGF表达具有极显著正相关性(r=0.413,P<0.01)。应用COX回归模型进行多变量分析并采用向前逐步回归法,仅浸润深度、uPA表达和病理类型对淋巴结转移有影响。结论uPA,uPAR,PAI-1及VEGF蛋白在直肠癌组织中表达增强,uPA,uPAR与直肠癌浸润转移密切相关。
Objective To study the expression of uPA, uPAR, PAI-1 and VEGF in urokinase-type plasminogen activator system in rectal cancer and its relationship with the biological behavior of rectal cancer. Methods From January 2005 to January 2006, the expression of uPA, uPAR, PAI-1 and VEGF protein in 67 cases of rectal cancer and its adjacent tissues were detected by immunohistochemical SP method. The clinicopathological data were retrospectively analyzed . Results The positive rates of uPA, uPAR, PAI-1 and VEGF protein in cancer and pericancerous tissue were significantly increased (P <0.01). The positive products mainly distributed in the cytoplasm of cancer cells. Invasion and serosal positive rate was significantly higher than the serosa group (P = 0.000,0.014,0.016,0.000). The positive rate of uPA and uPAR protein in lymph node metastasis group was significantly higher than that in non-lymph node metastasis group (P = 0.002, 0.008). The positive rate of PAI-1 protein in poorly differentiated group was significantly lower than that in moderately differentiated and well differentiated group (P <0.05). The positive rate of uPA, uPAR and VEGF protein in rectal cancer tissue differentiation was no significant difference. There was a significant positive correlation between uPA and uPAR protein expression in rectal cancer (r = 0.653, P <0.001). Of the 41 cases with uPA and uPAR protein positive at the same time, 28 cases had lymph node metastasis, and the incidence of metastasis was significantly higher than that of the negative group (4/15) (P <0.01). The expression of uPA in rectal cancer tissues was positively correlated with VEGF expression (r = 0.300, P <0.05). There was a significant positive correlation between PAI-1 protein expression and VEGF expression (r = 0.413, P <0.01). Multivariate analysis using the COX regression model and using forward stepwise regression, only the depth of invasion, uPA expression and pathological type of lymph node metastasis. Conclusion The expression of uPA, uPAR, PAI-1 and VEGF protein in rectal cancer tissues is enhanced. The expression of uPA and uPAR is closely related to the invasion and metastasis of rectal cancer.