Expression of microsomal prostaglandin E2 synthase-1 and its role in human hepatocellular carcinoma.

Microsomal prostaglandin E2 synthase-1 (mPGES1), an inducible enzyme similar to cyclooxygenase-2, functions downstream of cyclooxygenase-2 in the synthesis of prostaglandin E2. It contributes to carcinogenesis in a variety of tumors. Here, mPGES1 expression was assessed using immunohistochemistry of tissue microarrays containing a total of 100 hepatocellular carcinoma (HCC) tissue samples, 100 peritumoral liver tissue samples, and 13 normal liver tissue samples. The expression of mPGES1 was significantly increased in the HCC tissue samples (P < .001), relative to normal liver tissue. Second, there was a significant positive correlation between mPGES1 expression and the Barcelona Clinic Liver Cancer stage (P < .001) in HCC tissue samples. This correlation was also observed with encapsulation (P = .004) and portal vein thrombosis (P < .001). In addition, the lentiviral vector (Lv-mPGES1-shRNA), which down-regulates mPGES1, inhibited tumor growth in an HCC animal model. Taken together, mPGES1 expression was associated with multiple malignant characteristics and enhanced tumorigenesis in HCC and may serve as an important clinical and pharmacologic biomarker.