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Molecular and clinical characterization of TMEM71 expression at the transcriptional level in glioma

机译:胶质瘤中转录水平TMEM71表达的分子和临床特征

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Background Glioma is the most common and aggressive type of primary brain tumor in adults. Although radiotherapy and chemotherapy are used in the treatment of glioma, survival remains unsatisfactory. Chemoresistance is one of the primary reasons for the poor prognosis of glioma. Several studies have demonstrated that glioma stem cells (GSC) may be one of the reasons for chemoresistance. In this article, we attempt to search for a new biomarker related to GSC and chemoresistance in glioma. Methods We used three datasets (GSE23806, COSMIC, and CGGA) to search for the genes related to GSC, temozolomide (TMZ) resistance, and overall survival. The selected gene was investigated with respect to the relationship between mRNA levels and clinical characteristics in the CGGA and TCGA dataset. Gene ontology (GO) analysis was used for bioinformatics analysis. Kaplan‐Meier survival analysis and Cox regression analysis were used for survival analysis. Results The transmembrane protein 71 (TMEM71) gene was selected for further research. TMEM71 was highly expressed in GSCs and TMZ‐resistant cells. The TMEM71 mRNA levels increased with increasing grades of glioma. In IDH‐wild‐type and MGMT‐unmethylated samples, TMEM71 was overexpressed. The TMEM71 transcript levels were also increased significantly in mesenchymal subtype gliomas. GO analysis demonstrated that TMEM71 was related to the immune and inflammatory responses, cell proliferation, cell migration, chemotaxis, and the response to drugs. Specifically, PD‐1, PD‐L1, TIM‐3, and B7‐H3 were tightly associated with TMEM71 expression. This result indicates that TMEM71 may play an important role in the immune response. More importantly, high expression of TMEM71 was correlated with short survival time in both glioma and glioblastoma patients. Conclusion In summary, TMEM71 expression was increased in GBM and associated with immune response. Our study suggests that TMEM71 may function as an oncogene and serve as a new effective therapeutic target for the treatment of glioma.
机译:背景技术脑胶质瘤是成人中最常见和侵袭性的原发性脑肿瘤。尽管放疗和化学疗法被用于治疗神经胶质瘤,但是存活率仍然不能令人满意。化学耐药是胶质瘤预后不良的主要原因之一。多项研究表明,神经胶质瘤干细胞(GSC)可能是化学耐药的原因之一。在本文中,我们尝试寻找与神经胶质瘤中GSC和化学抗性相关的新生物标记。方法我们使用三个数据集(GSE23806,COSMIC和CGGA)搜索与GSC,替莫唑胺(TMZ)耐药性和总生存期相关的基因。针对CGGA和TCGA数据集中的mRNA水平与临床特征之间的关系,研究了所选基因。基因本体论(GO)分析被用于生物信息学分析。 Kaplan-Meier生存分析和Cox回归分析用于生存分析。结果选择了跨膜蛋白71(TMEM71)基因进行进一步研究。 TMEM71在GSC和TMZ耐药细胞中高表达。 TMEM71 mRNA水平随着神经胶质瘤等级的增加而增加。在IDH野生型和MGMT未甲基化的样品中,TMEM71过表达。在间充质亚型神经胶质瘤中,TMEM71转录水平也显着增加。 GO分析表明,TMEM71与免疫和炎症反应,细胞增殖,细胞迁移,趋化性以及对药物的反应有关。具体来说,PD-1,PD-1,TIM-3和B7-H3与TMEM71表达紧密相关。该结果表明TMEM71可能在免疫应答中起重要作用。更重要的是,在胶质瘤和胶质母细胞瘤患者中,TMEM71的高表达与生存时间短有关。结论总的来说,TMEM71在GBM中表达增加,并与免疫反应有关。我们的研究表明,TMEM71可能起癌基因的作用,并成为治疗神经胶质瘤的新有效治疗靶标。

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