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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Integrative transcriptomic and bioinformatics analysis identifies COL3A1 as a prognostic biomarker associated with
Miraj Ud Din1, Sajjad Ahmad2, Lai Xiangdong1
1State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Abstract:
Glioblastoma is one of the most common types of brain tumors and is a major health issue. The treatment remains a significant concern despite the significant advancements in chemotherapy, radiotherapy, and surgery, as the survival rate of the patients is still very low. To address this issue, our study aimed to identify potential biomarkers associated with glioblastoma by analyzing gene expression data related to the disease. A dataset with the accession number (GSE68848), containing the samples of glioblastoma patients and healthy individuals, was retrieved from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) analysis revealed that 1987 genes (751 upregulated and 1236 downregulated) were significantly expressed, with collagen type III alpha 1 chain (COL3A1) having the highest FC value (4.5367). The Gene Set Enrichment Analysis revealed the involvement of upregulated genes in cancer-associated pathways, including the Hallmark Epithelial-Mesenchymal Transition pathway, Hallmark G2M Checkpoint, and Hallmark Hypoxia. The protein network and functional interaction highlighted the involvement of the COL3A1 gene in glioblastoma. Gene expression and survival analysis were conducted using the GEPIA2 server to identify gene expression patterns and their effects in various types of tumors. To perform the structure evaluation, the COL3A1 3D structure was retrieved from the UniProt database and was docked to a library of anticancer compounds during molecular docking analysis. The compound (CMNPD14924) from the library showed the best binding score (-5.8051); therefore, this ligand was considered potentially essential for inhibiting the protein function. Molecular dynamics simulation revealed the effective binding of the ligand and protein. These outcomes suggest a key role for COL3A1 in glioblastoma progression. Exploration of downregulated genes is important, as these genes may also be involved in the disease advancement.
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