[Expression and clinical significance of coagulate and fibrolysis factors in tissue and plasma from hepatocellular carcinoma patients].
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 (Chi(2)=6.05, P=0.014; Chi(2)=4.29, P=0.038; Chi(2)=4.40, P=0.036).


CONCLUSIONS
TF, uPA, uPAR might have synergetic effect in invasion and metastasis of HCC, and they might relate to prognosis.
Zhou
Qi
Q
Department of General Surgery, Huangpu Branch of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510700, P. R. China. hnzhouqi@163.com
Liang
Li-Jian
LJ
Peng
Bao-Gang
BG
Zhen
Yu-Yang
YY
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011169:Portal Vein; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D013925:Thromboplastin; D014568:Urokinase-Type Plasminogen Activator