The oncogene brachyury (TBXT) is a T-box transcription factor that is overexpressed in multiple solid tumors and is associated with tumor aggressiveness and poor patient prognosis. Gliomas comprise the most common and aggressive group of brain tumors, and at the present time the functional and clinical impact of brachyury expression has not been investigated previously in these neoplasms. Brachyury expression (mRNA and protein) was assessed in normal brain (n = 67), glioma tissues (n = 716) and cell lines (n = 42), and further in silico studies were undertaken using genomic databases totaling 3115 samples. Our glioma samples were analyzed for copy number (n = 372), promoter methylation status (n = 170), and mutation status (n = 1569 tissues and n = 52 cell lines) of the brachyury gene. The prognostic impact of brachyury expression was studied in 1524 glioma patient tumors. The functional impact of brachyury on glioma proliferation, viability, and cell death was evaluated both in vitro and in vivo. Brachyury was expressed in the normal brain, and significantly downregulated in glioma tissues. Loss of brachyury was associated with tumor aggressiveness and poor survival in glioma patients. Downregulation of brachyury was not associated with gene deletion, promoter methylation, or inactivating point mutations. Brachyury re-expression in glioma cells was found to decrease glioma tumorigenesis by induction of autophagy. These data strongly suggest that brachyury behaves as a tumor suppressor gene in gliomas by modulating autophagy. It is important to note that brachyury constitutes an independent positive biomarker of patient prognosis. Our findings indicate that the role of brachyury in tumorigenesis may be tissue-dependent and demands additional investigation to guide rational interventions. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

---

T-box转录因子brachyury在神经胶质瘤中起着抑癌作用。

癌基因近距离性抽搐（TBXT）是T-box转录因子，在多种实体瘤中过表达，与肿瘤侵袭性和患者预后不良有关。神经胶质瘤是最常见和侵袭性的脑肿瘤，目前，尚未在这些肿瘤中研究过腕膜表达的功能和临床影响。在正常大脑（n = 67），神经胶质瘤组织（n = 716）和细胞系（n = 42）中评估了Brachyury表达（mRNA和蛋白质），并使用基因组数据库（共3115个样本）进行了进一步的计算机研究。分析了我们的神经胶质瘤样品的腕果肉基因的拷贝数（n = 372），启动子甲基化状态（n = 170）和突变状态（n = 1569组织和n = 52个细胞系）。在1524例脑胶质瘤患者的肿瘤中研究了近距表达的预后影响。在体外和体内均评价了腕果蝇对神经胶质瘤增殖，生存力和细胞死亡的功能影响。Brachyury在正常大脑中表达，在神经胶质瘤组织中明显下调。在神经胶质瘤患者中，短臂神经丢失与肿瘤的侵袭性和较差的存活率有关。心动过速的下调与基因缺失，启动子甲基化或失活点突变无关。发现胶质瘤细胞中Brachyury重新表达可通过诱导自噬减少胶质瘤的发生。这些数据有力地表明，近足动物在神经胶质瘤中通过调节自噬而起抑癌基因的作用。重要的是要注意，近距离骑行构成患者预后的独立阳性生物标志物。我们的研究结果表明，腕毛瘤在肿瘤发生中的作用可能是组织依赖性的，需要进一步研究以指导合理的干预措施。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版