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

Hum Pathol. 2013 Aug;44(8):1681-7. doi: 10.1016/j.humpath.2013.04.007. Epub 2013 Jun 20.

Abstract

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.

Keywords: Animal model; Hepatocellular carcinoma; Microsomal prostaglandin E2 synthase-1 (mPGES1); RNA interference; Tissue microarrays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor / analysis
  • Blotting, Western
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Intramolecular Oxidoreductases / biosynthesis*
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Staging
  • Prostaglandin-E Synthases
  • Tissue Array Analysis
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases