Abstract
BackgroundGlioma 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.MethodsRT-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.ResultsARL3 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.ConclusionsLow 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.
Highlights
Glioma is the most common primary intracranial tumor in adults and is notorious for its malignancy and unfavorable prognosis [1]
a>]. Intratumoral heterogeneityADP-ribosylation factor-like 3 (ARL3) is expressed at low levels in glioma a previous study has shown that ARL2 inhibits glioma proliferation and tumorigenicity by downregulating AXL [28], the functions of other ADP-ribosylation factor (ARL) members in glioma remained unknown
The results revealed that ARL3 mRNA levels decreased in both grade IV (GBM) and grade II samples in comparison with those in nontumor tissues (Fig. 1b)
Summary
Glioma is the most common primary intracranial tumor in adults and is notorious for its malignancy and unfavorable prognosis [1]. As a member of the ARF family, ARL3 has been reported to regulate cell morphology and cytokinesis through microtubule-based processes [17]. ARL3 influences ciliogenesis and is involved in ciliary function affecting kidney and photoreceptor development in mice [21, 22]. 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. The functional role of ARL3 in cancer remains unknown. We aimed to explore ARL3 expression and its roles in glioma prognosis
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