摘要
背景与目的:研究表明凝血及纤溶因子改变与恶性肿瘤的发生、发展密切相关。本研究检测组织因子(tissuefactor,TF)、尿激酶型纤溶酶原激活物(urokinase-typeplasminogenactivator,uPA)及其受体(urokinase-typeplasminogenactivatorreceptor,uPAR)在肝细胞癌(hepatocellularcarcinoma,HCC)组织中及血浆中的表达并探讨其临床意义。方法:应用酶联免疫吸附法(ELISA)检测肝细胞癌患者50例及对照组30例非癌患者的血浆TF、uPA和uPAR水平;50例肝癌中随机选取27例取其肝癌组织、癌旁组织,以27例非癌患者肝组织为对照,利用RT-PCR法分别检测TF、uPA、uPARmRNA的阳性率及相对表达强度,并结合临床病理资料进行分析。结果:肝细胞癌患者血浆TF、uPA及uPAR水平均较对照组升高[(409.4±13.0)pg/mlvs.(318.8±69.1)pg/ml,(1.63±0.52)ng/mlvs.(1.20±0.40)ng/ml,(1.36±1.00)ng/mlvs.(0.68±0.28)ng/ml],均有显著性差异(P<0.05)。肝细胞癌患者血浆TF水平在低分化组、肿瘤较大组及合并肝硬化组均显著升高(P<0.05),血浆uPA水平只在合并肝硬化组升高(P<0.05)。肝细胞癌患者血浆TF、uPA和uPAR水平在有淋巴结转移、肝外脏器转移及门脉癌栓组较无转移及无癌栓组升高(P<0.05)。TF、uPA、uPARmRNA在肝细胞癌组织中阳性率及相对表达强度分别为62.96%(17/27)、70.37%(19/27)、77.78%(21/27)及0.57±0.27、0.96±0.46、0.78±0.32,均显著高于癌旁组织及非癌患者肝组织,均有显著性差异(P<0.05);TF、uPA、uPARmRNA在有肝内转移及门脉癌栓组的阳性率及相对表达强度均高于无肝内转移及门脉癌栓组(P<0.05)。经Pearson检验,肝细胞癌患者TF、uPA和uPARmRNA表达呈正相关(TF/uPA:r=0.37,P<0.01,TF/uPAR:r=0.53,P<0.01,uPA/uPAR:r=0.36,P<0.01)。经Cox多因素分析三者均为独立预后因素[TF(χ2=6.05,P=0.014),uPA(χ2=4.29,P=0.038),uPAR(χ2=4.40,P=0.036)]。结论:TF、uPA及uPAR可能在肝细胞癌的侵袭转移过程中起协同作用;三者可能与肝癌患者预后有关。
BACKGROUND ＆ OBJECTIVE：Considerable evidences showed that changes of coagulation and proteolysis factors are closely related to the genesis and growth of malignancy. This study was to detect the expression of tissue factor （TF）, urokinase-type plasminogen activator （uPA）, and urokinase-type plasminogen activator receptor （uPAR） in cancer tissues and plasma of patients with hepatocellular carcinoma （HCC）, and analyze their prognostic significance. METHODS. Blood samples were obtained from 50 HCC patients and 30 patients with non-tumor disease. Plasma levels of TF, uPA, and uPAR were detected by ELISA. Cancer tissue and adjacent tissue samples were obtained randomly from 27 patients in HCC group; normal liver tissue samples were also collected from 27 patients in benign disease group. The mRNA levels of TF, uPA, and uPAR in all tissue samples were detected by reverse transcription-polymerase chain reaction （RT-PCR）. Their correlations to clinicopathologic features of HCC were analyzed. RESULTS. Plasma levels of TF, uPA, and uPAR were significantly higher in HCC group than in control group [（409.4±13.0） pg/ml vs. （318.8±69.1） pg/ml, （1.63±0.52） ng/ml vs. （1.20±0.40） ng/ml, （1.36±1.00） ng/ml vs. （0.68±0.28） ng/ml, P〈0.05]. Poor differentiation, larger size, and cirrhosis of HCC increased plasma TF level （P〈0.05）; cirrhosis also increased plasma uPA level （P〈0.05）; lymphatic metastasis, extrahepatic metastasis, and portal venous tumor thrombus （PVTT） increased plasma levels of TF, uPA, and uPAR （P〈0.05）. The positive rates of TF, uPA, and uPAR in HCC tissues were 62.96%, 70.37%, 77.78%, respectively; the mRNA levels of TF, uPA, and uPAR were 0.57＋0.27, 0.96＋ 0.46, 0.78＋0.32, respectively. The positive rates and mRNA levels of TF, uPA, and uPAR were all significantly higher in HCC tissues than in adjacent tissues and normal liver tissues （P〈0.05）. Intrahepatic metastasis and PVTT increased the positive rate and mRNA levels of TF, uPA, and uPAR in HCC （P〈0.05）. Pearson test showed that TF expression was positively correlated to uPA, and uPAR expression （r=0.373, P〈0.01; r=0.534, P〈0.01）; uPA expression was positively correlated to uPAR expression （r= 0.365, P〈0.01）. COX regression analyses showed that TF, uPA, and uPAR were independent prognostic factors of HCC （χ^2=6.05, P=0.014; χ^2=4.29, P=0.038;χ^2=4.40, P=0.036）. CONCLUSION：TF, uPA, uPAR might have synergetic effect in invasion and metastasis of HCC, and they might relate to prognosis.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2006年第11期1433-1438,共6页
Chinese Journal of Cancer
基金
广东省医学科学技术研究基金项目(No.B2006035)
广东省自然科学基金(No.06300808)~~
