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

IF 5.3 2区材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Applied Nano Materials Pub Date : 2019-06-24 DOI:10.1186/s12967-019-1914-3

Yulin Wang, Weijiang Zhao, Xin Liu, Gefei Guan, Minghua Zhuang

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引用次数: 19

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.

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ARL3在胶质瘤中下调并作为预后生物标志物。

背景:胶质瘤是成人最常见的原发性恶性脑肿瘤，预后较差。ARL3是ARF家族的一员，在纤毛功能和脂质修饰蛋白转运中起关键作用。据报道，ARL3参与睫状体疾病，影响肾脏和光感受器的发育。然而，ARL3在癌症中的功能作用尚不清楚。在本研究中，我们旨在探讨ARL3的表达及其在胶质瘤预后中的作用。方法:采用RT-PCR和免疫组化检测胶质瘤组织中ARL3的表达水平。利用肿瘤基因组图谱(TCGA)、中国胶质瘤基因组图谱(CGGA)和脑瘤分子数据库(REMBRANDT)的数据研究ARL3的表达及其在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年生存率的nomogram。最后，通过基因本体分析(GO)、基因集富集分析(GSEA)和基因集变异分析(GSVA)对其生物学功能进行探讨。结果:ARL3在胶质瘤中表达下调，且与胶质瘤患者预后不良相关。c指数、ROC曲线下面积和nomogram校正图显示对胶质瘤患者具有有效的预测能力。此外，GO和通路分析表明ARL3参与微环境中的血管生成和免疫细胞浸润。结论:低ARL3表达预示预后不良，并与GBM微环境中抗血管生成和浸润免疫细胞比例有关。因此，ARL3可能是胶质瘤的预后标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Nano Materials Multiple-

CiteScore

8.30

自引率

3.40%

发文量

1601

期刊介绍： ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.