PDF(Pubmed)
Abstract：
Lower-grade gliomas (GBMLGG) are common, fatal, and difficult-to-treat cancers. The current treatment choices have impressive efficacy constraints. As a result, the development of effective treatments and the identification of new therapeutic targets are urgent requirements. Disulfide metabolism is the cause of the non-apoptotic programmed cell death known as disulfideptosis, which was only recently discovered. The mRNA expression data and related clinical information of GBMLGG patients downloaded from public databases were used in this study to investigate the prognostic significance of genes involved in disulfideptosis. In the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohort, our findings showed that many disulfidptosis-related genes were expressed differently in normal and GBMLGG tissues. It was discovered that IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a key gene that influences the outcome of GBMLGG. Besides, a nomogram model was built to foresee the visualization of GBMLGG patients. In addition, in vivo and in vitro validation of IQGAP1\'s cancer-promoting function was done. In conclusion, we discovered a gene signature associated with disulfideptosis that can effectively predict OS in GBMLGG patients. As a result, treating disulfideptosis may be a viable alternative for GBMLGG patients.
摘要：
低级别胶质瘤（GBMLGG）很常见，致命的,和难以治疗的癌症。目前的治疗选择具有令人印象深刻的疗效限制。因此,迫切需要开发有效的治疗方法和确定新的治疗靶点。二硫化物代谢是非凋亡性程序性细胞死亡的原因，称为二硫化物凋亡，这是最近才发现的。本研究使用从公共数据库下载的GBMLGG患者的mRNA表达数据和相关临床信息来研究参与二硫化物沉积的基因的预后意义。在癌症基因组图谱（TCGA）和基因表达综合（GEO）队列中，我们的发现表明，许多与二硫键凋亡相关的基因在正常和GBMLGG组织中表达不同。发现含有IQ基序的GTP酶激活蛋白1（IQGAP1）是影响GBMLGG结果的关键基因。此外,建立了一个列线图模型来预测GBMLGG患者的可视化。此外,对IQGAP1的促癌功能进行了体内和体外验证。总之,我们发现了一个与二硫键沉积相关的基因标签,它可以有效预测GBMLGG患者的OS.因此,治疗二硫键下垂可能是GBMLGG患者的可行替代方案。
