Trefoil factor 1 (TFF1) is a potential prognostic biomarker with functional significance in breast cancers

Breast cancer (BC) is the most common cancer in women and the second leading cause of their cancer death. Establishing an accurate BC prognosis is very difficult because of its heterogeneity. Elevated TFF1 levels in serum were associated with development of BC, TFF1 expression was upregulated in BC compared to the healthy breast tissue. The aim of this study was to investigate the function of TFF1 in BCs, and to assess whether serum TFF1 could be used in formulating a prognosis for BC patients. In silico analyses were carried out to determine the expression of TFF1 mRNA in different types of BC and the association between TFF1 expression and survival of BC patients. Expression of TFF1 protein was checked in 52 paraffin-embedded tissues of BCs by immunochemistry, and serum concentration of TFF1 in 70 BC patients and 32 healthy controls was measured by ELISA. Functional activities of TFF1 in BC cells were determined by CCK-8 assay, colony formation, BrdU-DNA synthesis, and assays for migration and invasion. Results showed that expression of TFF1 mRNA was correlated with expression of biomarkers of luminal cancers including ESR1, GATA3, FOXA1, MYB and XBP1. In addition, patients with ER⁺BC had higher expression of TFF1 than those with ER^- (p < 0.05). There was also lower expression of TFF1 in triple-negative breast cancer (TNBC) than in non-TNBC (p < 0.05), which corresponds with the level of serum TFF1 in TNBC patients, compared with non-TNBC patients (p < 0.001). Furthermore, expression of TFF1 was associated with tumor size (p = 0.002), nodal status (p < 0.001), histological grade (p < 0.001), ER status (p = 0.012), PR status (p < 0.001) and HER2 (p < 0.001), while serum TFF1 was only statistically different among BC with ER⁺, PR ⁺ and HER2⁺ (p = 0.04139, 0.0018, 0.0004). Elevated TFF1 expression correlated with increased overall survival of BC patients (p = 0.00068). Finally, TFF1 was found to inhibit the cell growth, colony formation, migration and invasion of BC cells in vitro. All these results suggest that expression of TFF1 was related to ER status of BC and that expression of TFF1 was lower in TNBC than in non-TNBC. TFF1 was found to inhibit proliferation, migration and invasion of BC cells in vitro. Expression of TFF1 was associated with clinical characters of patients with BC. Serum TFF1 could be used to predict prognosis of patients with BC, especially non-TNBC.