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Identifying FBLN1 (Gene ID: 2192) as a Potential Melanoma Biomarker for Melanoma based on an Analysis of microRNA Expression Profiles in the GEO and TCGA Databases.

Genet Test Mol Biomarkers. 2021 Jan;25(1):68-78. doi:10.1089/gtmb.2020.0274
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摘要


We analyzed and compared the gene expression profiles (GSE92763) from normal melanocytes with malignant melanoma cell lines to identify genes that were differentially expressed that could serve as potential biomarkers for melanoma diagnosis. Gene expression profiles from the GSE92763 dataset were downloaded from the Gene Expression Omnibus (GEO) database. By comparing normal human melanocytes with multiple melanoma cell lines we identified 127 differentially expressed genes whose expression was altered. These data were used to identify hub genes associated with protein-protein interaction networks using Cytoscape software. To explore the biological functions of the aforementioned hub genes, we utilized the clusterProfiler package in R studio to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We then used the Gene Expression Profiling Interactive Analysis (GEPIA) website to determine the association of these hub genes with overall survival (OS). In addition, we utilized the Oncomine and Line Encyclopedia (CCLE) databases to further analyze and compare the expression of these key genes associated with melanoma with other tumor types. The hub genes included three upregulated and seven downregulated genes, which were linked with extracellular junctions, migration, paracrine and proliferation functions based on GO. In addition, we performed a confirmatory analysis of the hub genes using The Cancer Genome Atlas (TCGA) database. This analysis revealed that the expression of the Fibulin 1 (FBLN1; gene ID: 2192) gene was significantly downregulated in melanomas, and that its expression level in melanoma patients was significantly associated with OS with high expressors having better OS (log-rank p = 0.0034, hazard ratio = 1.5, p = 0.0036). We further analyzed the expression of FBLN1 in melanoma using the TCGA and Oncomine databases, and confirmed that FBLN1 is expressed at lower levels than in other cells (p = 2.03E-15, t = -15.586). FBLN1 has extremely high DNA copy number and low messenger RNA expression in melanoma cell lines according to the CCLE analysis. These results suggest that FBLN1 expression may be utilized as a biomarker and essential prognostic factor for melanoma; as well as provide an important theoretical basis for the development of melanoma treatments.

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