Expression Of Cyclooxygenase-2 (COX-2) In Human Primary Hepatocellular Carcinoma And Their Relationship With PCNA,P27,P21,P15,P16 Protein

Background:Hepatocellular carcinoma (HCC) often arises from a background of long-standing chronic inflammatory liver diseases. Several lines of evidence suggest that mediators of inflammation, such as prostaglandins (PGs), may be involved causally in its pathogenesis. The synthesis of PGs is controlled by coordinated activation of eicosanoid-forming enzymes including cyclooxygenases (COXs). Three isoforms of COX have been identified: COX-1, COX-2 and COX-3. COX-2 is not constitutively expressed, but is induced by a variety of stimuli such as cytokines, hormones, mitogens, and growth factors, which explains its up-regulation in various inflammatory diseases and human cancers.Evidence has shown that COX-2-generated PGs promote tumor cell proliferation, survival, and angiogenesis. For example, COX-2 overexpression in cultured cells leads to increased cell survival. Knockout of the COX-2 gene can suppress tumorigenesis in mice that have a genetic predisposition to form polyps. In animal studies, enhanced COX-2 expression in mammary gland and skin induces tumorigenesis. These findings strongly suggest the importance of COX-2-cntrolled PGmetabolism in the development and progression of human cancers.Despite increase expression of COX-2 in human liver cancer, inhibition of liver cancer growth by Nonsteroidal anti-inflammatory drugs (NSAIDs), and the documented role of COX-2 in human cancers in general, the direct biologic role and molecular mechanism of COX-2-mediated prostanoids in the control of liver cancer growth have not been established with molecular approach. Objectives:1. To study the expression of Cyclooxygenase-2 (COX-2) in human primary hepatocellular carcinoma (HCC)2. To study the expression of PCNA in human primary hepatocellular carcinoma ( HCC ) and its relationship with cyclooxygenase-2(COX-2) .3. To study the expression of P27, P21, P15, P16 in human primary hepatocellular carcinoma ( HCC ) and its relationship with cyclooxygenase-2 ( COX-2 ) and cyclooxygenase-2 ( COX-2 )Methods:1. Expression of COX-2 was detected immunohistochemically.2. The results were analyzed by computer-aided image analysis system.3. Group statistic was analyzed by Fisher's Exact Test or T-Test (P<0.05), correlation coefficient was analyzed by Pearson correlation (P<0.05).Results:1. The rate of COX-2 expression, the rate of area of COX-2 expression, the value of greay of COX-2 expression in HHCs were respectively significantly different from those in paracancerous tissues (P<0.05).2. The rate of PCNA expression, the rate of area of PCNA expression in HCCs were respectively significantly different from those in paracancerous tissues (P<0.05). The rate of PCNA expression in COX-2-positive group was significantly different from that in the negative group (P<0.05). There is correlation between the rate of area of COX-2 expression and the rate of area of PCNA expression in HCCs and paracancerous tissues (P<0.05).3. The rate of P27 expression, the rate of area of P27 expression in HCCs were respectively significantly different from those in paracancerous tissues ( P<0.05 ). The rate of P27 expression in COX-2-positive group was not significantly different from that in the negative group (P>0.05). There is no correlation between the rate of area of COX-2 expression and the rate of area of P27 expression in HCCs and paracancerous tissues (P>0.05). The rate of P16 expression, the rate of area of P16 expression in HCCs were respectively significantly different from those in paracancerous tissues ( P<0.05 ). The rate of P16 expression in COX-2-positive group was significantly different from that in the negative group (P<0.05). There is negative correlation between the rate of area of COX-2 expression and the rate of area of P16 expression inHCCs and paracancerous tissues. P21, P15 underexpress in HCCs and paracancerous tissues. Conclusions:1. COX-2 is overexpressed in human primary hepatocellular carcinoma.2. PCNA is overexpressed in human primary hepatocellular carcinoma, which is correlated with the l...