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

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1100-1108
Number of pages9
JournalGastric Cancer
Volume22
Issue number6
DOIs
StatePublished - Nov 1 2019

Keywords

  • FBXW7
  • Gastrointestinal stromal tumor
  • High risk
  • Notch 1
  • c-myc

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

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