Background: Trefoil factor 3 (TFF3) is a small molecule secreted by the mammalian gastrointestinal tract and is overexpressed in some human malignant tumors. We investigated the prognostic values of immunohistochemical (IHC) TFF3 expression and serum TFF3 levels in patients with gastric cancer, and whether TFF3 influenced tumor proliferation and invasion in vitro. Methods: We examined 111 patients who underwent R0 gastrectomy for gastric cancer between April 2012 and April 2015. IHC TFF3 expression and serum TFF3 levels were evaluated regarding their associations with clinicopathological factors and recurrence-free survival (RFS). In vitro cell proliferation and migration assays were used to explore the biological role of TFF3 in human gastric cancer cell lines following transfection with a lentivirus-based shRNA plasmid. Results: IHC TFF3 expression showed significant associations with depth of invasion (p = 0.024), lymph node metastasis (p = 0.008), and RFS (log-rank p = 0.002). Serum TFF3 levels were correlated with IHC TFF3 expression (p = 0.013). RFS was significantly poorer in patients with high (n = 27) compared to low (n = 84) serum TFF3 levels (log-rank p = 0.003). Cox multivariate analysis indicated that serum TFF3 level was an independent prognostic factor for RFS (p = 0.024). In vitro assays, TFF3 downregulation significantly inhibited both proliferation and invasion of gastric cancer cells. Conclusions: Serum TFF3 levels could be useful prognostic markers in patients with gastric cancer. TFF3 may play various biological roles in proliferation and invasion of gastric cancer cells.
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