Integrin alpha nu beta 6 Protein Expression and Prognosis in Solid Tumors: A Meta-Analysis

摘要

Background and Objective Integrins are a family of adhesion receptor proteins that provide signaling from the extracellular matrix to the cytoplasm. They have been associated with cancer by promoting migration, invasion, metastasis, and survival. alpha nu beta 6 integrin is upregulated in several tumors. Here, we evaluate the prognostic impact of alpha nu beta 6 integrin protein expression in solid tumors. Methods A systematic search of electronic databases identified publications exploring the effect of alpha nu beta 6 integrin on overall survival (OS). Hazard ratios (HRs) were pooled in a meta-analysis using generic inverse variance and random effects modeling. Subgroup analyses were conducted based on tumor site, tumor stage, antibody used for immunohistochemistry (IHC) and method for extraction of the HR. A meta-regression explored the influence of clinical variables on the magnitude of effect of alpha nu beta 6 integrins on OS. Results Seventeen studies comprising 5795 patients met the inclusion criteria. High alpha nu beta 6 integrin expression in tumors was associated with worse OS (HR 1.65, 95% confidence interval [CI] 1.32-2.06; Cochran's Q p < 0.001, I-2 = 81%). Adverse outcomes were similar in all tumor sites (subgroup difference p = 0.10), with the strongest association between alpha nu beta 6 integrins and OS in gastric cancer (HR 2.20, 95% CI 1.71-2.83) and the lowest in head and neck cancer (HR 1.21, 95% CI 0.79-1.83). There was no significant difference between early-stage and metastatic cancer, type of IHC antibodies, and analysis methods. Conclusions High expression of alpha nu beta 6 integrins is associated with adverse survival outcome in several tumors. Prospective studies evaluating the prognostic impact of alpha nu beta 6 integrin and its role as a therapeutic target are warranted.