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

Abstract

IntroductionCyclooxygenase-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 methodsIdentification 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.ResultsA 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).ConclusionsThis 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.

COX-2/PGE2 Axis Regulates HIF2α Activity to Promote Hepatocellular Carcinoma Hypoxic Response and Reduce the Sensitivity of Sorafenib Treatment

“…The COX-2/PGE2 axis is a potential driver of HIF-2α expression and activity in HCC cells and HCC tissues under hypoxic conditions COX-2 is also upregulated in hypoxic HCC tissues and is associated with a poor prognosis in HCC patients; this relationship with HCC is similar to that of HIF-2α (10,11,16,18). COX-2 elicits its effects mainly through producing prostaglandins, especially PGE2 (20,21).…”

“…Previous studies have also revealed that COX-2 can be induced by various stimuli, including hypoxia (15,16). In the context of HCC, COX-2 expression in tumour tissues is closely associated with the spontaneous initiation, development and treatment effects of HCC (17)(18)(19). As the predominant product of COX-2, prostaglandin E2 (PGE2) can achieve diverse biological effects primarily through its binding to a family of receptors to promote angiogenesis, cell survival and the metastasis of cancer cells (20,21).…”

Use of cyclooxygenase inhibitor and the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A nested case‐control study using a nationwide population‐based data

“…In vitro, the increased expression of COX‐2 in HCC was associated with tumour differentiation, tumour growth and apoptosis . Chen et al reported that the expression of COX‐2 in patients with HCC is related to decreased overall survival and disease‐free survival in patients with HCC. A randomized controlled trial showed that use of meloxicam prevents the recurrence of HCC after curative therapy .…”

Isoalantolactone inhibits IKKβ kinase activity to interrupt the NF‐κB/COX‐2‐mediated signaling cascade and induces apoptosis regulated by the mitochondrial translocation of cofilin in glioblastoma

“…COX‐2‐selective inhibitors can inhibit the inflammatory response, cell proliferation, and angiogenesis and can induce cancer cell apoptosis. Previous studies have indicated that the overexpression of COX‐2 in glioma cells could affect the development of glioma, and an increase in COX‐2 expression is also associated with the histopathological grade and invasiveness of glioma, which ultimately lead to poor prognoses for patients . In general, reducing the expression of COX‐2 may be an effective alternative to inhibit glioma growth and promote apoptosis.…”