ARL3 在神经胶质瘤中下调并作为预后生物标志物。

ARL3 is downregulated and acts as a prognostic biomarker in glioma.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, 515041, Guangdong, China.

Center for Neuroscience, Shantou University Medical College, Shantou, 515041, Guangdong, China.

出版信息

J Transl Med. 2019 Jun 24;17(1):210. doi: 10.1186/s12967-019-1914-3.

Abstract

BACKGROUND

Glioma is the most common primary malignant brain tumor in adults with a poor prognosis. ARL3 is a member of the ARF family, and plays a key role in ciliary function and lipid-modified protein trafficking. ARL3 has been reported to be involved in ciliary diseases, in which it affects kidney and photoreceptor development. However, the functional role of ARL3 in cancer remains unknown. In this study, we aimed to explore ARL3 expression and its roles in glioma prognosis.

METHODS

RT-PCR and immunohistochemistry were performed to examine the expression level of ARL3 in glioma samples. Data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Repository for Molecular Brain Neoplasia Data (REMBRANDT) databases were employed to investigate ARL3 expression and its roles in glioma prognosis. A nomogram for predicting 3- or 5-year survival was established using Cox proportional hazards regression. Finally, gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were performed to explore the biological function.

RESULTS

ARL3 expression was downregulated in glioma, and associated with poor prognosis in glioma patients. The C-indexes, areas under the ROC curve and calibration plots of the nomogram indicated an effective predictive performance for glioma patients. In addition, GO and pathway analyses suggested the involvement of ARL3 in angiogenesis and immune cell infiltration in the microenvironment.

CONCLUSIONS

Low ARL3 expression predicted poor prognosis and contributed to antiangiogenesis and the proportion of infiltrating immune cells in the GBM microenvironment. Thus, ARL3 may be a prognostic marker and therapeutic target for glioma.

摘要

背景

脑胶质瘤是成人中最常见的原发性恶性脑肿瘤,预后较差。ARL3 是 ARF 家族的成员,在纤毛功能和脂修饰蛋白转运中发挥关键作用。已有报道称 ARL3 参与纤毛病,影响肾脏和光感受器发育。然而,ARL3 在癌症中的功能作用尚不清楚。在这项研究中,我们旨在探讨 ARL3 的表达及其在脑胶质瘤预后中的作用。

方法

采用 RT-PCR 和免疫组织化学方法检测脑胶质瘤样本中 ARL3 的表达水平。利用癌症基因组图谱(TCGA)、中国脑胶质瘤基因组图谱(CGGA)和分子脑肿瘤数据库(REMBRANDT)数据库的数据,探讨 ARL3 的表达及其在脑胶质瘤预后中的作用。采用 Cox 比例风险回归建立预测 3 年或 5 年生存的列线图。最后,进行基因本体(GO)分析、基因集富集分析(GSEA)和基因集变异分析(GSVA),以探讨其生物学功能。

结果

ARL3 在脑胶质瘤中表达下调,与脑胶质瘤患者的不良预后相关。列线图的 C 指数、ROC 曲线下面积和校准图表明,其对脑胶质瘤患者具有有效的预测性能。此外,GO 和通路分析表明,ARL3 参与了血管生成和肿瘤微环境中免疫细胞浸润。

结论

ARL3 低表达预测预后不良,并促进 GBM 微环境中的血管生成和浸润免疫细胞的比例。因此,ARL3 可能是脑胶质瘤的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f378/6591946/0cc35f01e206/12967_2019_1914_Fig1_HTML.jpg

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