Prognostic significance of cyclooxygenase-2 expression in patients with hepatocellular carcinoma: a meta-analysis

INTRODUCTION: Cyclooxygenase-2 (COX-2) is believed to be an important enzyme in the carcinogenesis of hepatocellular carcinoma (HCC). However, it is still controversial whether COX-2 expression can be regarded as a prognostic factor for HCC patients. We performed a systematic review and meta-analysis of studies assessing the clinical and prognostic significance of COX-2 expression in HCC. MATERIAL AND METHODS: Identification and review of publications assessing clinical or prognostic significance of COX-2 expression in HCC until November 1, 2014. A meta-analysis was performed to clarify the association between COX-2 expression and clinical outcomes. RESULTS: A total of 11 publications met the criteria and included 943 cases. Analysis of these data showed that COX-2 expression was not significantly correlated with capsular formation (OR = 0.84, 95% confidence interval (CI): 0.46–1.55, p = 0.58), tumor TNM stage (OR = 0.73, 95% CI: 0.23–2.33, p = 0.59), vascular invasion (OR = 1.04, 95% CI: 0.25–4.35, p = 0.96), tumor size (OR = 0.78, 95% CI: 0.21–2.86, p = 0.71), or tumor differentiation degree (OR = 1.08, 95% CI: 0.42–2.79, p = 0.87). However, in the identified studies, COX-2 expression was strongly associated with high alpha-fetoprotein level (OR = 1.83, 95% CI: 1.01–3.33, p = 0.05), HBsAg status (OR = 1.85, 95% CI: 1.13–3.03, p = 0.01), decreased overall survival (relative risk (RR): 1.54, 95% CI: 1.18–2.02, p = 0.001) and decreased disease-free survival (RR = 1.49, 95% CI: 1.22–1.81, p < 0.001). CONCLUSIONS: This meta-analysis shows that COX-2 expression in HCC is associated with decreased overall and disease-free survival and thus marks a worse prognosis. Nevertheless, more large sample and well-designed studies are warranted to confirm this finding.