Poor prognosis in cholangiocarcinoma patients with low FBXW7 expression is improved by chemotherapy

Ishii,Norihiro; Araki,Kenichiro; Yokobori,Takehiko; Watanabe,Akira; Tsukagoshi,Mariko; Kubo,Norio; Suzuki,Hideki; Saito,Fumiyoshi; Altan,Bolag; Hosouchi,Yasuo; Shirabe,Ken; Kuwano,Hiroyuki

doi:10.3892/ol.2017.5946

Poor prognosis in cholangiocarcinoma patients with low FBXW7 expression is improved by chemotherapy

Authors:
- Norihiro Ishii
- Kenichiro Araki
- Takehiko Yokobori
- Akira Watanabe
- Mariko Tsukagoshi
- Norio Kubo
- Hideki Suzuki
- Fumiyoshi Saito
- Bolag Altan
- Yasuo Hosouchi
- Ken Shirabe
- Hiroyuki Kuwano
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Affiliations: Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Molecular Pharmacology and Oncology, Gunma University, Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Surgery and Laparoscopic Surgery, Gunma Prefecture Saiseikai‑Maebashi Hospital, Maebashi, Gunma 371‑0821, Japan, Department of Hepatobiliary and Pancreatic Surgery, Gunma University, Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan
Published online on: March 29, 2017 https://doi.org/10.3892/ol.2017.5946
Pages: 3653-3661
Copyright: © Ishii et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The tumor suppressor FBXW7 has been demonstrated to degrade several oncoproteins, including c‑Myc. Although low FBXW7 expression levels are suggested to be a poor prognostic factor in a number of types of solid tumor, the role of FBXW7 in chemosensitivity is controversial. The purpose of the present study was to determine whether FBXW7 expression may be used as a marker for poor prognosis and chemosensitivity in patients with cholangiocarcinoma (CC). FBXW7 expression was investigated by immunohistochemistry in 100 surgically resected CC samples, and the association between FBXW7 expression, clinicopathological factors and prognosis was evaluated. Nuclear FBXW7 expression tended to be lower compared with normal tissues. A total of 54 patients exhibited high expression levels of FBXW7, and 46 patients exhibited low expression levels. Patients with low FBXW7 expression possessed significantly larger tumors (P=0.049), enhanced expression of c‑Myc and Ki‑67 and significantly poorer prognoses compared with those with high FBXW7 expression (P=0.016). Multivariate analysis revealed that low FBXW7 expression was an independent negative prognostic factor in CC (P=0.043). In patients with high FBXW7 expression levels, the cancer‑specific survival times were not significantly different between patients with or without chemotherapy. However, in patients with low FBXW7 expression levels, the cancer-specific survival times were significantly longer in subjects who underwent chemotherapy compared with those who did not (P=0.001). These data suggest that FBXW7 status in CC is a useful predictor of poor prognosis and cancer progression. Additionally, FBXW7 may be a surrogate marker to predict the efficacy of chemotherapy in CC.

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