Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma

Yokobori,Takehiko; Mimori,Koshi; Iwatsuki,Masaaki; Ishii,Hideshi; Tanaka,Fumiaki; Sato,Tetsuya; Toh,Hiroyuki; Sudo,Tomoya; Iwaya,Takeshi; Tanaka,Yoichi; Onoyama,Ichiro; Kuwano,Hiroyuki; Nakayama,Keiichi   I.; Mori,Masaki

doi:10.3892/ijo.2012.1436

Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma

Authors:
- Takehiko Yokobori
- Koshi Mimori
- Masaaki Iwatsuki
- Hideshi Ishii
- Fumiaki Tanaka
- Tetsuya Sato
- Hiroyuki Toh
- Tomoya Sudo
- Takeshi Iwaya
- Yoichi Tanaka
- Ichiro Onoyama
- Hiroyuki Kuwano
- Keiichi I. Nakayama
- Masaki Mori
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Affiliations: Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan, Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan , Department of Surgery, Saitama Prefectural Cancer Center, Saitama, Japan, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan, Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-8511, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan
Published online on: April 19, 2012 https://doi.org/10.3892/ijo.2012.1436
Pages: 253-259

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Abstract

FBXW7 is a tumor suppressor gene that plays a role in cell cycle regulation via Myc degradation. However, the clinical significance of FBXW7 in esophageal squamous cell carcinoma (ESCC) has not been evaluated. The purpose of this study was to assess the clinical significance of FBXW7 for prognosis in human ESCC. Real-time RT-PCR was used to examine the expression of FBXW7 to determine its clinicopathological significance in 75 cases of ESCC. Overall survival rate was calculated using the Kaplan-Meier method, while multivariate survival was analyzed with the Cox hazard model. FBXW7 suppression analysis was performed to examine proliferation potency and Myc expression in the FBXW7 siRNA groups. The relationship between FBXW7 expression and the copy number loss of FBXW7 was examined in clinical samples of ESCC. Finally, FBXW7 copy number loss was linked to prognosis in 42 ESCC patients. FBXW7 expression in cancer was lower compared to non-cancer tissues (P=0.003) and is an independent prognostic factor. The proliferation rates and Myc protein expression were significantly enhanced in FBXW7 siRNA cells compared to the controls. Cases with a loss of FBXW7 copy number had low FBXW7 expression and a poorer prognosis than cases with no loss of copy number. Genetic alterations in esophageal cancer lead to the loss of FBXW7 expression and increased cell proliferation. These genetic alterations of FBXW7 status may provide a prognostic factor for ESCC patients.