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

Abstract

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.

Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma

“…There is growing evidence that cancer-related inflammation plays crucial roles in the process of tumorigenesis and progression in various malignant tumors, mainly via enhancing angiogenesis and metastasis, suppressing adaptive immune responses, and reducing reactions to chemotherapeutic drugs [14,15]. High expression of inflammation-related enzymes, proteins, or chemokine receptors in osteosarcoma has been already verified by various studies to correlate with poor outcomes, such as cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), heat shock proteins (HSPs), and chemokine (C-X-C motif) receptor 4 (CXCR4) [16][17][18][19][20]. In addition, the administration of anti-inflammatory drugs during chemotherapy has been confirmed to prolong patients' survival [21].…”

Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1

“…Chemoprevention may involve the perturbation of a variety of steps in tumor initiation, promotion and progression. As such, COX-2 overexpression leads to cancer cell proliferation, neovascularization, and suppression of apoptosis and thus is associated with a worse prognosis in various malignancies, especially sarcomas [ 14 , 15 , 16 ]. It is therefore not surprising that overexpression of COX-2 has also been observed in NF1-associated MPNSTs and that selective COX-2 inhibition had an antitumor effect on these cells [ 30 ].…”

“…A potential strategy to circumvent these challenges is to discover new uses for compounds with an established track record of safe and long-term use in humans, alone or in combination with already known cancer prevention agents, such as widely used cyclooxygenase-2 (COX-2) inhibitors, whose anti-neoplastic effects are mediated through the inhibition of angiogenesis via decreasing COX-2-induced vascular endothelial growth factor (VEGF) production [ 11 ] and apoptosis via altered caspase signaling [ 12 , 13 ]. Notably, COX-2 overexpression has been found in a variety of sarcomas and has been associated with poor prognosis [ 14 , 15 , 16 ], thus suggesting that COX-2 inhibitors could play a role in NF1 cancer prevention.…”

Immunohistochemical detectability of cyclooxygenase‐2 expression in cells of human melanocytic skin lesions: A methodological review

“…In turn, the COX-2 peroxidase activity may contribute to production of mutagens ( Figure 1). [5][6][7][8] Enhanced COX-2 expression was demonstrated in various types of human malignancies: carcinomas of colon, 9,10 breast, 11,12 lung, 13,14 stomach, 15,16 esophagus, 17,18 pancreas, 19 bladder, 20 prostate, 21 ovary, 22,23 cervix, 24,25 osteosarcomas, 26,27 gliomas, 28,29 and Hodgkin lymphomas. 30 In most of the studies, it was shown that cancer progression is accompanied by an increase in COX-2 levels and may have prognostic potential.…”