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Erschienen in: Gastric Cancer 6/2019

11.03.2019 | Original Article

The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors

verfasst von: Yuki Koga, Masaaki Iwatsuki, Kohei Yamashita, Yuki Kiyozumi, Junji Kurashige, Toshiro Masuda, Kojiro Eto, Shiro Iwagami, Kazuto Harada, Takatsugu Ishimoto, Yoshifumi Baba, Naoya Yoshida, Nobutomo Miyanari, Hiroshi Takamori, Jaffer A. Ajani, Hideo Baba

Erschienen in: Gastric Cancer | Ausgabe 6/2019

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Abstract

Background

Few reliable prognostic markers have been established despite elucidation of the molecular mechanisms of gastrointestinal stromal tumor (GIST) development. We evaluated F-box and WD repeat domain-containing 7 (FBXW7), a cell-cycle-regulating and tumor suppressor, in GISTs. We aimed to determine the clinical relevance of FBXW7 in GISTs and characterize the molecular mechanism of FBXW7 in a GIST cell line.

Methods

We measured FBXW7 expression in 182 GIST cases, correlated the expression levels with clinicopathological features, and characterized the molecular mechanism underlying suppressed FBXW7 expression in GIST cells in vitro.

Results

Of the 182 GISTs, 98 (53.8%) and 84 (46.2%) were categorized in the high and low FBXW7 expression groups, respectively. Compared with the high FBXW7 expression group, the low expression group showed a significantly poorer prognosis in terms of recurrence-free (P = 0.01) and overall (P = 0.03) survival. FBXW7 expression was a significant independent factor affecting the 10-year recurrence-free survival rate (P = 0.04). In vitro, FBXW7-specific siRNAs enhanced c-myc and Notch 1 protein expression and upregulated cell proliferation, invasion, and migration.

Conclusion

FBXW7 is a potential predictive marker of recurrence after curative resection of GISTs. FBXW7 expression may help identify patients benefitting from adjuvant therapy more precisely compared with a conventional risk stratification model.
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Metadaten
Titel
The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors
verfasst von
Yuki Koga
Masaaki Iwatsuki
Kohei Yamashita
Yuki Kiyozumi
Junji Kurashige
Toshiro Masuda
Kojiro Eto
Shiro Iwagami
Kazuto Harada
Takatsugu Ishimoto
Yoshifumi Baba
Naoya Yoshida
Nobutomo Miyanari
Hiroshi Takamori
Jaffer A. Ajani
Hideo Baba
Publikationsdatum
11.03.2019
Verlag
Springer Singapore
Erschienen in
Gastric Cancer / Ausgabe 6/2019
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-019-00950-y

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