Loss of Fbxw7 expression is a predictor of recurrence in colorectal liver metastasis

Background/Purpose
Fbxw7 is a tumor suppressor through ubiquitination and degradation of multiple oncoproteins. Loss of Fbxw7 is frequently observed in various human cancers. In this study, we examined the role of Fbxw7 expression in colorectal liver metastasis (CRLM) and its mechanism.
Methods
Fifty-six patients with CRLM who undergo curative resection were enrolled. Fbxw7 in tumor tissue was determined by immunohistochemistry. Patients were divided into two groups, the Fbxw7 high and low group. Clinicopathological factors including miR-223 expression were compared between the high (n=32) and low Fbxw7 group (n=24).
Results
Fbxw7 expression in tumor tissues was significantly lower than that in normal tissues. The disease-free survival in the low Fbxw7 group was significantly worse than that in the high Fbxw7 group, and 3years disease-free survival of the low and the high Fbxw7 group were 12.5% and 47.0%, respectively (p=0.023). On multivariate analysis, loss of Fbxw7 was detected as one of the independent risk factor for recurrence of CRLM (Hazard ratio: 2.390, p=0.017). Likewise, Fbxw7 expression inversely correlated to miR-223 expression (p=0.017).
Conclusion
Loss of Fbxw7 in tumor tissues could be a reliable predictor of recurrence after hepatectomy in patients with CRLM, and miR223 might be a possible regulator of Fbxw7.

内容要旨・審査要旨・論文本文の公開
本論文は, 著者Yoichiro Kawashitaの学位論文として提出され, 学位審査・授与の対象となっている。
著者の申請により要約(2018-01-11公開)に替えて論文全文を公開(2018-10-17)