The Role of FBXW7, a Cell-cycle Regulator, As a Predictive Marker of Recurrence of Gastrointestinal Stromal Tumors

Overview

Journal Gastric Cancer

Specialties Gastroenterology
Oncology

Date 2019 Mar 12

PMID 30854619

Citations 6

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.

Wang W, Liu X, Zhao L, Jiang K, Yu Z, Yang R Front Pharmacol. 2025; 15:1505027.

PMID: 39749199 PMC: 11694028. DOI: 10.3389/fphar.2024.1505027.

YAP acts as an independent prognostic marker and regulates growth and metastasis of gastrointestinal stromal tumors via FBXW7-YAP pathway.

Wu X, Yamashita K, Matsumoto C, Zhang W, Ding M, Harada K J Gastroenterol. 2024; 60(3):275-284.

PMID: 39557657 DOI: 10.1007/s00535-024-02180-1.

FBXW7 regulates the sensitivity of imatinib in gastrointestinal stromal tumors by targeting MCL1.

Wu X, Iwatsuki M, Takaki M, Saito T, Hayashi T, Kondo M Gastric Cancer. 2023; 27(2):235-247.

PMID: 38142463 DOI: 10.1007/s10120-023-01454-6.

The significance of CDT1 expression in non-cancerous and cancerous liver in cases with hepatocellular carcinoma.

Ogawa M, Moriyama M, Midorikawa Y, Nakamura H, Shibata T, Kuroda K J Clin Biochem Nutr. 2023; 73(3):234-248.

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Comprehensive characterization of FBXW7 mutational and clinicopathological profiles in human colorectal cancers.

Liu Y, Chen H, Bao H, Zhang J, Wu R, Zhu L Front Oncol. 2023; 13:1154432.

PMID: 37064111 PMC: 10091464. DOI: 10.3389/fonc.2023.1154432.

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