A Bioinformatic Analysis Revealed Novel Targets for Ameloblastoma: Potential Genes Expression and Targeted Signaling Pathway
Kata Kunci:
Ameloblastoma, FGFR2, BRAF, KRAS, MAPK signaling pathwayAbstrak
Introduction: Ameloblastoma is a rare odontogenic neoplasm of the mandible and maxilla, aggressive local growth and high recurrence rate. It is important to identify various genes expressed causing deregulations and molecular alterations. This study aimed to investigate the potential genes involved in pathogenesis of Ameloblastoma and targeted therapy by in silico analysis.
Literature review: Bioinformatic analysis were performed by identified genes expressed through GeneCards database and characterised via Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-protein interactions (PPI) and hub genes were visualized using STRING-Cytoscape, followed by in silico analysis using MalaCards database to determine targeted therapy. The analysis showed a count of top 10 genes were commonly expressed in ameloblastoma: EGFR, MTOR, FGFR2, FGFR1, FGFR3, BRAF, MAP2K1, KRAS, TP53, MMP2. The genes play role to regulate cell differentiation, protein binding and cell development. PPI and hub genes showed significant interaction of FGFR2, BRAF, and KRAS through the MAPK (Mitogen-Activated Protein Kinase) signaling pathway. Trametinib and Dabrafenib administration were investigated as targeted therapy to prevent recurrence or malignant transformation of ameloblastoma.
Discussion: Pathogensis of Ameloblastoma may stop by down-regulating mutated genes and blocking the enzymes needed for tumor cell growth as well. MAPK signaling pathway also targeted for ameloblastoma therapy. Trametinib and Dabrafenib are both antineoplastic and protein kinase inhibitor agent which cause apoptosis, inhibit cell proliferation or prevent the proliferation of neoplasms.
Conclusion: FGFR2, BRAF, and KRAS play important role in pathogenesis of Ameloblastoma through MAPK signaling pathway. Trametinib and Dabrafenib were approved for drug candidate.
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