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p53-Altered FBXW7 Expression Determines Poor Prognosis in Gastric Cancer Cases

¹ Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan; ² Departments of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan; ³ Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; ⁴ Department of Surgery, National Cancer Center Hospital, Tokyo, Japan; and ⁵ Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan

Requests for reprints: Masaki Mori, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan. Phone: 81-6-6879-3251; Fax: 81-6-6879-3259; E-mail: mmori{at}gesurg.med.osaka-u.ac.jp.

Key Words: FBXW7 • gastric cancer • tumor suppressor gene

A molecular target associated with the progression of gastric cancer has not yet been uncovered. FBXW7 is a tumor suppressor gene transcriptionally controlled by p53 that plays a role in the regulation of cell cycle exit and reentry via c-Myc degradation. Few studies have addressed the clinical significance of FBXW7 expression in gastric cancer. Therefore, we examined FBXW7 mRNA expression to determine its clinicopathologic significance in 100 cases of gastric cancer. Low expression levels of FBXW7 in primary gastric cancer contributed to malignant potential, such as lymph node metastasis (P = 0.0012), tumor size (P = 0.0003), and poor prognosis (P = 0.018). In comparison with 52 cases of gastric cancer without the p53 mutation, 29 cases with the mutation exhibited lower expression levels of FBXW7 (P = 0.0034), revealing a significant relationship between p53 mutation and FBXW7 expression. Furthermore, we found that gastric cancer patients who had low FBXW7 expression levels and p53 mutation had a distinctively poor prognosis in comparison with other subgroups (P = 0.0033). In conclusion, we showed a role for p53 in the transcriptional regulation of FBXW7 expression in clinical gastric cancer cases and showed that disruption of both p53 and FBXW7 contributes to poor prognosis. [Cancer Res 2009;69(9):3788–94]