The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors
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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.
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.
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.
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.
KeywordsGastrointestinal stromal tumor FBXW7 c-myc Notch 1 High risk
The authors thank Dr. Takihiro Kamio, Dr. Reiji Muto and Dr. Toshihiko Murayama for providing clinical samples. The authors also thank Dr. Miyake and Ms. Ogata for their excellent technical assistance.
This work was supported in part by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (Grant numbers 16K10463 and 16KK0184).
Compliance with ethical standards
Conflict of interest
We have no conflicts of interest to declare.
Ethics approval and consent to participate
Ethics approval of this study was granted by the ethics committee at Kumamoto University Hospital (approval number 2212) The study was conducted in accordance with the Declaration of Helsinki principles.