FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in triple-negative breast cancer

Abstract

Aims Forkhead box O (FOXO) transcription factors, consisting of FOXO1, FOXO3a, FOXO4 and FOXO6, are involved in carcinogenesis and tumour progression. Recent studies have suggested that FOXOs act as tumour suppressors in a variety of human cancers. This study investigated the clinicopathological significance of FOXOs in triple-negative breast cancer (TNBC).Methods FOXO protein expressions were assessed by immunohistochemistry in 125 TNBC tissues. Correlations between FOXO protein expression and various clinicopathological parameters, including patients' survival, were investigated. MDA-MB-468 cell line was used for in vitro cell proliferation and migration assay.Results FOXO1 protein expression was not observed in all 125 TNBC tissues. FOXO4 and FOXO6 protein expressions were detected in 11 (8.8%) and 14 (11.2%) TNBC tissues, respectively. Loss of FOXO4 expression was significantly associated with high histological grade (P=0.014, (2) test), and TNBCs with positive FOXO6 expression correlated with high grade (P=0.020, (2) test). FOXO3a expression was detected in 40 (32%) TNBC cases and correlated with adverse clinicopathological features, such as lymph node metastasis (P=0.021, (2) test), perineural invasion (P=0.013, (2) test) and higher Ki-67 proliferation index (P=0.048, t-test). Additionally, FOXO3a expression was significantly associated with poor disease-free survival (P=0.015, log-rank test). In the in vitro study, siRNA-mediated FOXO3a knockdown in the MDA-MB-468 cell line inhibited cell proliferation and migration.Conclusion Among FOXO members, FOXO3a may have a potential role in promoting tumour cell migration and proliferation and may serve as a prognostic biomarker and a potential therapeutic target for TNBC.