Cyclooxygenase‐2 expression correlates with development, progression, metastasis, and prognosis of osteosarcoma: a meta‐analysis and trial sequential analysis

Cyclooxygenase‐2 (COX‐2), a key enzyme in arachidonic acid metabolism, is involved in several cancers, including osteosarcoma. The prognostic significance of COX‐2 in osteosarcoma remains controversial. This study was to analyze the potential clinical and prognostic effects of COX‐2 protein expression in patients with osteosarcoma. Eligible articles were searched via online databases. The combined odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were calculated using the random‐effects model. Trial sequential analysis (TSA) was applied to analyze the required information size and determine the reliability of the evidence. Twenty‐three studies on COX‐2 expression were identified, which included a total of 1084 patients with malignant osteosarcoma and 247 patients with benign osteochondroma. COX‐2 protein expression in osteosarcoma was higher than in benign osteochondroma (OR = 7.66, P < 0.001). COX‐2 expression was not correlated with age, gender, tumor location, cancer histology, or necrosis (P > 0.1), but was significantly associated with tumor grade (high grade vs. low grade: OR = 4.81, P < 0.001), clinical stage (stage 3–4 vs. stage 1–2: OR = 4.89, P < 0.001), and metastasis (yes vs. no: OR = 3.53, P < 0.001). Based on TSA results, we suggest that additional studies are not required to examine osteosarcoma vs. benign osteochondroma, tumor grade, clinical stage, or metastasis. No heterogeneity was observed in these analyses. COX‐2 expression is linked to poor prognosis in metastasis‐free survival, overall survival, and relapse‐free survival, as indicated by multivariate analysis. Therefore, the expression of COX‐2 may correlate with the development, progression, metastasis, and poor prognosis of osteosarcoma.