Exploring gene network and protein interaction analysis of neurotrophin signaling pathway in ameloblastoma.

Abstract

Ameloblastoma is a non-cancerous but aggressive oral tumor emerging from odontogenic epithelial tissue involved during odontogenesis. Since there is lack in unravelling the complete molecular pathogenesis of ameloblastoma, chemotherapy is less attempted and a lot of disagreement over the optimal treatment option. Hence, till date, wide surgical resection is considered to be the reliable treatment for ameloblastoma. The Neurotrophin Signaling pathway plays an important role in neuron signaling and it is closely related with the MAPK pathway, which on the other hand regulated cell differentiation, apoptosis, proliferation, plasticity and survival. Protein- Protein Interaction analysis was analysed with STRING tool using WNL value, identified that CTNNB1, HRAS, NGFR, NGFR, and SORT1 having high interacting with BDNF, NT4, p75NTR, NGF, and NT3. The results of ontology analysis revealed that Neurotrophin signaling pathway is associated with Cell surface receptor signaling pathway, regulation of cell differentiation, regulation of development process, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, PI3K-Akt signaling pathway and Ras signaling pathway leading to pathogenesis involving genes. Further, clustering coefficient values of proteins BDNF, NT4, p75NTR, NGF & NT3 were identified as 0.627, 0.708, 0.367, 0.644 & 0.415. The results of molecular docking studies revealed among the selected ligands Methyl-ɣ-oresellinate, N-(4-Hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, Atranorin and Oresellinate exhibited high binding affinity with selected protein. The key genes involved in Neurotrophin signaling pathway leading to ameloblastoma pathogenesis is revealed, which are closely associated with cell differentiation, cell proliferation, pro-apoptosis, and pro-survival regulations. Further it can be concluded that Neurotrophin signaling pathway could be one of the promising pathway to tailor the targeted drug therapy for Ameloblastoma treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-024-00223-2.