EGFR influences the resistance to targeted therapy in BRAF V600E melanomas by regulating the ferroptosis process

Abstract

To identify genes differentially expressed between resistant and sensitive BRAF V600E melanoma cell lines using bioinformatics tools applied to GEO data. We retrieved and downloaded the target gene set (GSE45558) from the GEO database and used R software to filter differentially expressed genes (DEGs) between BRAF V600E melanoma cell lines resistant. The identified DEGs were subjected to GO functional enrichment analysis (including biological processes, molecular functions, and cellular components) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, utilizing R software. Protein-protein interaction networks for the DEGs were generated using the STRING online database. Top hub genes were cross-referenced with genes related to ferroptosis from the FerrDb database to identify DEGs linked to ferroptosis in resistant melanoma cells. From the GEO database analysis, we identified the top 100 DEGs between BRAF V600E melanoma cell lines, including 50 downregulated and 50 upregulated DEGs. Using STRING and Cytoscape, we identified the top 10 hub genes: IL6, IL1B, CCL2, MMP2, TGFB2, EGFR, POSTN, SERPINE1, COL1A2, and MITF. Cross-referencing with the FerrDb database, we found that IL6 and EGFR are differentially expressed genes related to ferroptosis in resistant melanoma cells. Validation through clinical samples and in vitro experiments confirmed the high expression of the ferroptosis-related gene EGFR as a potential biomarker for resistance to targeted therapy in BRAF^V600E melanoma. Bioinformatics analysis identified key resistance genes in BRAF^V600E melanoma targeted therapy, demonstrating the impact of ferroptosis-related gene EGFR on the resistance of BRAF^V600E melanoma.