Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival

World J Gastroenterol. 2016 Oct 21;22(39):8798-8805. doi: 10.3748/wjg.v22.i39.8798.

Abstract

Aim: To determine whether cyclooxygenase-2 (COX-2) and prostaglandin E1 receptor (EP1) contribute to disease and whether they help predict prognosis.

Methods: We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma (HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffin-embedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined.

Results: Factors associated with poor overall survival (OS) were alpha-fetoprotein > 400 ng/mL, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues (Edmondson grade I-II) than in poorly differentiated tissues (Edmondson grade III-IV) (P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue (P = 0.001).

Conclusion: COX-2 expression appears to be linked to early HCC events (initiation), while EP1 receptor expression may participate in tumor progression and predict survival.

Keywords: Cyclooxygenase-2; Hepatocellular carcinoma; Liver resection; Prognosis; Prostaglandin E1 receptor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / mortality
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / metabolism*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Prostaglandin E, EP1 Subtype / metabolism*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • PTGER1 protein, human
  • Receptors, Prostaglandin E, EP1 Subtype
  • Cyclooxygenase 2
  • PTGS2 protein, human