Identification of ferroptosis-related proteins in ameloblastoma based on proteomics analysis

Abstract

Purpose: We used proteomic sequencing and experimental verification to identify the potential ferroptosis-related proteins in ameloblastoma.

Methods: Samples of ameloblastoma (n = 14) and normal gingival tissues (n = 5) were collected for proteomic sequencing to identify differentially expressed proteins (DEPs) in ameloblastoma. Ferroptosis-related genes were downloaded from FerrDb V2, which were then compared with DEPs to obtain ferroptosis-related DEPs (FR-DEPs). A functional enrichment analysis was performed, and a protein-protein interaction network was built. The hub proteins were screened using the Cytoscape software, and potential drugs targeting them were retrieved from the DrugBank database. A hub protein was selected for immunohistochemical validation, and its expression was assessed in ameloblastomas, odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. The primary ameloblastoma cells were cultured to explore the effect of the protein on the migratory properties of the tumour cells.

Results: A total of 58 FR-DEPs were screened, and six hub proteins were identified: mTOR, NFE2L2, PRKCA, STAT3, EGFR, and CDH1. Immunohistochemical analysis showed that mTOR expression was upregulated in ameloblastomas compared with that in odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. p-mTOR was highly expressed in ameloblastomas, with a positivity rate of 83.3%. In addition, rapamycin, an inhibitor of mTOR, can inhibit the migratory capacity of primary cultured ameloblastoma cells.

Conclusion: Our results revealed the ferroptosis-related proteins in ameloblastomas and their underlying biological processes. Additionally, mTOR was overexpressed and was found to be associated with the aggressiveness of ameloblastomas, which may be a potential target for future treatments.

Keywords: Ameloblastoma; Ferroptosis; Proteomics; mTOR.