The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors
The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors
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DOI：
10.1007/s10120-019-00950-y
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发表时间：
2019-11-01
期刊：
影响因子：
7.4
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
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作者：
Koga, Yuki;Iwatsuki, Masaaki;Baba, Hideo
背景
尽管胃肠道间质瘤（GIST）发生的分子机制已得到阐明，但可靠的预后标志物却很少被确定。我们对含F - box和WD重复结构域7（FBXW7）——一种细胞周期调节因子和肿瘤抑制因子在GIST中的情况进行了评估。我们旨在确定FBXW7在GIST中的临床相关性，并描述其在GIST细胞系中的分子作用机制。
方法
我们检测了182例GIST病例中FBXW7的表达情况，将其表达水平与临床病理特征相关联，并在体外对GIST细胞中FBXW7表达受抑制的分子机制进行了研究。
结果
在182例GIST中，分别有98例（53.8%）和84例（46.2%）被归入FBXW7高表达组和低表达组。与高表达组相比，低表达组在无复发生存（P = 0.01）和总生存（P = 0.03）方面预后明显更差。FBXW7表达是影响10年无复发生存率的一个重要独立因素（P = 0.04）。在体外，FBXW7特异性小干扰RNA增强了c - myc和Notch 1蛋白的表达，并上调了细胞增殖、侵袭和迁移能力。
结论
FBXW7是GIST根治性切除术后复发的一个潜在预测标志物。与传统的风险分层模型相比，FBXW7表达可能有助于更准确地识别出能从辅助治疗中获益的患者。
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.