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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
ARL3 is downregulated and acts as a prognostic biomarker in glioma
Yulin Wang1, Weijiang Zhao2, Xin Liu3
1Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, 515041, Guangdong, China.
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.
Insights
Low expression of ARL3, a protein involved in cell function, is linked to poor prognosis in glioma patients. This finding suggests ARL3 could be a potential therapeutic target for brain tumors.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioma is a common adult brain tumor with a poor prognosis.
- ARL3, an ARF family member, is crucial for ciliary function and protein trafficking.
- The role of ARL3 in cancer, particularly glioma, was previously unknown.
Purpose of the Study:
- To investigate the expression of ARL3 in glioma.
- To determine the prognostic significance of ARL3 in glioma patients.
- To explore the potential biological functions of ARL3 in glioma.
Main Methods:
- Examined ARL3 expression using RT-PCR and immunohistochemistry in glioma samples.
- Analyzed ARL3 expression and prognostic value in TCGA, CGGA, and REMBRANDT databases.
- Developed a nomogram for survival prediction and performed GO, GSEA, and GSVA for functional analysis.
Main Results:
- ARL3 expression was found to be downregulated in glioma tissues.
- Lower ARL3 expression correlated with a poorer prognosis in glioma patients.
- Nomogram performance indicated effective prediction of patient survival.
- Functional analyses suggested ARL3 involvement in angiogenesis and immune cell infiltration.
Conclusions:
- Downregulated ARL3 expression is associated with poor glioma prognosis.
- ARL3 may serve as a prognostic biomarker for glioma.
- ARL3 could be a potential therapeutic target for glioma, particularly glioblastoma (GBM).
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