Associação da expressão das proteínas COX-2, TNF-α, TLR4 e IKKα com a sobrevida de pacientes com carcinomas de células escamosas bucais : uma revisão sistemática

Abstract

Squamous cell carcinoma (SCC) is the most prevalent malignant neoplasm of the oral cavity, with significant rates of morbidity and mortality. The role of inflammation in tumor initiation, growth, and progression, as well as in the survival of patients with oral cancer is still unclear. Given the large number of researches evaluating the relationship of inflammatory markers with oral cancer and the heterogeneity of results, we developed a systematic review and meta-analysis to investigate the evidence regarding the association of the tumor necrosis factor α (TNF-α), toll-like receptor 4 (TLR4), I𝜅B kinase α (IKKα) and cyclo-oxygenase 2 (COX-2) with the survival of patients with oral SCC (OSCC). A systematic review was conducted in the electronic databases of PubMed, Web of Science, LILACS, EMBASE, Scopus, and Cochrane Library by two independent researchers. The PECO question was “Does the overexpression of tumor necrosis factor α, cyclooxygenase 2, I𝜅B α kinase or toll-like Receptor 4 influence the survival of patients with OSCC?”. Prospective and/or retrospective observational studies that evaluated the association of the expression of the cited markers with the outcomes of overall survival, disease-specific survival, disease-free survival, survival probability, and 5-year survival were selected. Twentyone articles met the eligibility criteria for inclusion in the systematic review, as being fifteen on COX-2, three on TLR4, two on IKKα, and one about TNF-α. Three studies that address the COX-2 marker presented sufficient data to develop a meta-analysis. The estimated hazard ratio (HR) was 1.51 (95% CI 0.97, 2.33) for the association of COX-2 overexpression with the overall survival outcome, however, this was not statistically significant (p=0.07). Low heterogeneity was observed among the studies evaluated in the meta-analysis (I2=0%). The number of included studies that evaluated the TNF-α, TLR4, and IKKα markers was insufficient to develop a meta-analyzes. The results point to a probable positive association between the expression of the aforementioned markers and lower survival rates of patients with OSCC. Although the included articles present promising results, broader cohort studies should be carried out to validate the use of the cited markers as prognostic factors.