Prognostic value of high FOXO3a expression in patients with solid tumors: A meta-analysis and systematic review

Abstract

Background: FOXO3a (previously termed FKHRL1), plays an evolutionarily conserved role in the control of biological process, including DNA damage, apoptosis, and cell cycle regulation. However, the role of FOXO3a in tumors remains controversial. This meta-analysis was conducted to evaluate the prognostic value of FOXO3a expression in patients with solid tumors. Methods: A systematic literature search of the PubMed, Web of Science, Embase, and Cochrane Library databases was performed. Eligible publications on FOXO3a and cancer prognosis were collected and screened according to the eligibility criteria. The combined odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were used to assess the prognostic value of FOXO3a. Stata 12.0 software was used for statistical analysis. Results: A total of 4058 patients from 21 articles on a variety of solid tumors were included. Meta-analysis showed that the increased FOXO3a expression level was associated with longer overall survival (HR = 0.62; 95% CI: 0.46–0.85). The pooled ORs indicated high expression level of FOXO3a in tumors was significantly associated with lymph node metastasis (OR = 0.46; 95% CI: 0.30–0.71), TNM stage (OR = 0.37; 95% CI: 0.25–0.54), tumor differentiation (OR = 0.46; 95% CI: 0.26–0.80), distant metastasis (OR = 0.44; 95% CI: 0.32–0.61), and age (OR = 1.28; 95% CI: 1.08–1.51). However, we did not observe a significant correlation between the high expression of FOXO3a and sex or tumor size. Conclusions: The high expression level of FOXO3a was associated with better clinical outcomes in solid tumors. FOXO3a may therefore serve as a potential prognostic biomarker and a promising molecular target.