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Prognostic Value of Trefoil Factor 3 Expression in Patients with Gastric Cancer

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Abstract

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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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, Japan

    Yoshiki Taniguchi, Yukinori Kurokawa, Tsuyoshi Takahashi, Jota Mikami, Yasuhiro Miyazaki, Koji Tanaka, Tomoki Makino, Makoto Yamasaki, Kiyokazu Nakajima, Masaki Mori & Yuichiro Doki

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  1. Yoshiki Taniguchi
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  2. Yukinori Kurokawa
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  5. Yasuhiro Miyazaki
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Corresponding author

Correspondence to Yukinori Kurokawa.

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All authors declare that they have no conflict of interest.

Ethical standards

The study was approved by the ethics committee of the Institutional Review Board.

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Supplementary Fig. 1.

Expression levels of pSTAT3/STAT3, pMAPK/MAPK, and β-actin in OCUM-1 and KATO III cells transfected with a lentivirus-based shRNA TFF3 plasmid or a negative control lentivirus-based shRNA plasmid (PPTX 123 kb)

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Taniguchi, Y., Kurokawa, Y., Takahashi, T. et al. Prognostic Value of Trefoil Factor 3 Expression in Patients with Gastric Cancer. World J Surg 42, 3997–4004 (2018). https://doi.org/10.1007/s00268-018-4737-0

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  • DOI: https://doi.org/10.1007/s00268-018-4737-0

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