Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

Mascaux, Céline; Martin, Benoı̂t; Paesmans, Marianne; Berghmans, Thierry; Dusart, Michelle; Haller, Annick; Lothaire, Philippe; Meert, Anne-Pascale; Lafitte, Jean-Jacques; Sculier, Jean-Paul

doi:10.1038/sj.bjc.6603226

Cited by 52 publications

(33 citation statements)

References 42 publications

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“…High expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M2 (RRM2), and thymidylate synthase (TS) were suggested as negative prognostic factors for patients with resected NSCLC (33,34). In addition, cyclooxygenase-2 and amplification of the actin-4 (ACTN4) gene were considered markers for a poor prognosis in stage I disease (35,36). However, a conceivable prognostic biomarker for patients with stage I AD has not yet been established.…”

Section: Univariate Analysis Multivariate Analysismentioning

confidence: 99%

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

et al. 2017

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Abstract. AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and migration, is also associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated the prognostic significance of the expression of AXL and/or its ligand, growth arrestspecific 6 (GAS6), in completely resected lung AD. We evaluated the relationship between AXL, GAS6, and vimentin expression, as determined by immunohistochemistry (IHC) analysis, with overall survival and disease-free survival in 113 patients with stages I-III lung AD. Protein expression was also assayed using western blot analysis in 10 lung AD cell lines. AXL-positive (AXL

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Section: Univariate Analysis Multivariate Analysismentioning

confidence: 99%

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

et al. 2017

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“…28,66,127 Similarly, the prognostic significance of COX-2 expression in other types of human cancers is controversial, with some studies supporting COX-2 as a useful predictive factor and other studies refuting such a role. 4,26,29,46,61,70,83,103,117,131 In animal cancers, there is currently not enough information to clearly define the prognostic significance of COX-2 expression. In most studies addressing COX-2 expression in animal cancers, a follow-up of the subjects is not available.…”

Section: Prognostic Significance Of Cox-2 Expressionmentioning

confidence: 99%

Cyclooxygenase-2 Expression in Animal Cancers

Doré

2010

Vet Pathol

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Cyclooxygenase (COX; also known as prostaglandin endoperoxide synthase) is a key enzyme in the biochemical pathway leading to the synthesis of prostaglandins. A large amount of epidemiological and experimental evidence supports a role for COX-2, the inducible form of the enzyme, in human tumorigenesis, notably in colorectal cancer. COX-2 mediates this role through the production of PGE 2 that acts to inhibit apoptosis, promote cell proliferation, stimulate angiogenesis, and decrease immunity. Similarly, COX-2 is believed to be involved in the oncogenesis of some cancers in domestic animals. Here, the author reviews the current knowledge on COX-2 expression and role in cancers of dogs, cats, and horses. Data indicate that COX-2 upregulation is present in many animal cancers, but there is presently not enough information to clearly define the prognostic significance of COX-2 expression. To date, only few reports document an association between COX-2 expression and survival, notably in canine mammary cancers and osteosarcomas. Some evidence suggests that COX inhibitors could be useful in the prevention and/or treatment of certain cancers in domestic animals, the best example being urinary transitional cell carcinomas in dogs. However, determination of the levels of COX-2 in a tumor does not appear to be a good prognostic factor or a good indicator for the response to nonsteroidal anti-inflammatory drug therapy. Clearly, additional research, including the development of in vitro cell systems, is needed to determine if COX-2 expression can be used as a reliable prognostic factor and as a definite therapeutic target in animal cancers.

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“…Completely resected adenocarcinomas with high COX-2 expression were associated with shortened patient survival in the series by Achiwa et al (30) In a recent metaanalysis, Mascaux et al found that high COX-2 expression was associated with a trend for shorter survival in NSCLC patients, particularly with early-stage disease (31,32). In preclinical models, high COX-2 expression is antiapoptotic, stimulates epithelial cell growth and invasion, and leads to EGFR TKI resistance through activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway (15, 33 -36).…”

Section: Discussionmentioning

confidence: 99%

The Potential Predictive Value of Cyclooxygenase-2 Expression and Increased Risk of Gastrointestinal Hemorrhage in Advanced Non–Small Cell Lung Cancer Patients Treated with Erlotinib and Celecoxib

Fidler

Argiris

Patel

et al. 2008

Clinical Cancer Research

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Purpose: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, potentiates antitumor effects of erlotinib in preclinical studies, and COX-2 is frequently expressed in non^small cell lung cancer (NSCLC).With these observations, we designed a phase II trial to evaluate the efficacy and safety of erlotinib plus celecoxib in advanced NSCLC. Experimental Design: Previously treated stage IIIB/IV NSCLC patients were given celecoxib at 400 mg orally twice daily and erlotinib at 150 mg orally daily until disease progression. Planned accrual was 40 patients. Tissue was collected for epidermal growth factor receptor (EGFR) analysis and COX-2 immunohistochemistry. Results: Twenty-six patients were enrolled (17 men, 9 women; median age, 66 years). Eighteen and 21patients had tissue available for EGFR analysis and COX-2 immunohistochemistry, respectively. The median progression-free survival (PFS) and overall survival were 2.0 and 9.2 months, respectively. Eleven of 21 patients tested had increased tumor COX-2 expression, which was strongly associated with prolonged PFS (P = 0.048). Four patients on anticoagulation or with a history of peptic ulcer disease had grade 3/grade 4 upper gastrointestinal bleeding (GIB), prompting early study closure. Three patients with GIB had endoscopy that found peptic ulcers. Conclusions: The combination of erlotinib and celecoxib does not seem superior to erlotinib alone in unselected patients. However, longer PFS with high-tumor COX-2 expression suggests that trials of EGFR and COX-2 inhibitors may be warranted in this patient subset. GIB observed in our trial supports excluding patients with a history of peptic ulcer disease or those requiring therapeutic anticoagulation from future EGFR and COX-2 inhibitor studies.

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Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

Cited by 52 publications

References 42 publications

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

Cyclooxygenase-2 Expression in Animal Cancers

The Potential Predictive Value of Cyclooxygenase-2 Expression and Increased Risk of Gastrointestinal Hemorrhage in Advanced Non–Small Cell Lung Cancer Patients Treated with Erlotinib and Celecoxib

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