Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
Sci Rep. 2020 Sep 8;10(1):14767. doi: 10.1038/s41598-020-71719-y.
Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples (P < 0.0001). Sixty-four GISTs were stratified into high or low ETV1 mRNA expression groups based on the median relative abundance of ETV1 mRNA. The multivariate analysis showed that low ETV1 expression, as well as tumor size and mitotic index, was an independent factor of recurrence (hazard ratio: 8.1). Patients with high ETV1 expression achieved significantly longer recurrence-free survival (RFS) times than those with low ETV1 expression (P = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.
虽然大多数胃肠道间质瘤（GIST）具有诱导组成性信号转导的 KIT 突变，但临床结果是可变的。ETS 易位变体 1（ETV1）基因编码一种转录因子，据报道该转录因子与 GIST 中的 KIT 合作。然而，ETV1 的临床作用在很大程度上是未知的。本研究旨在研究 ETV1 表达及其与 GIST 临床特征的关系。我们进行了一项队列研究，纳入了 2008 年 10 月至 2015 年 2 月间接受手术切除的 64 例 GIST 患者。比较了 ETV1 mRNA 表达与非 GISTs 的表达，并在风险分类或临床结果中进行了分析。GIST 样本的 ETV1 mRNA 表达明显高于非 GIST 样本（P<0.0001）。根据 ETV1 mRNA 的中位数相对丰度，将 64 例 GIST 分为高或低 ETV1 mRNA 表达组。多变量分析显示，低 ETV1 表达以及肿瘤大小和有丝分裂指数是复发的独立因素（风险比：8.1）。高 ETV1 表达的患者无复发生存时间明显长于低 ETV1 表达的患者（P=0.025）。我们的研究表明，低 ETV1 表达是 GIST 患者手术后复发的独立因素，因此，低 ETV1 表达可能是侵袭性恶性 GIST 的标志物。
