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.
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Data availability
All the data used in the present study are available from the corresponding author upon reasonable request.
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Acknowledgements
We would like to thank Editage (www.editage.com) for English language editing.
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This study was supported by a grant-in-aid for the Project of Science and Technology of Hebei Province (no. 21377719D).
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Conception and design were contributed by HL and XL; Manuscript was drafted by HL and XM; Provision of study materials or patients was contributed by SM, XZ and XL; All experiments were completed by HL, XM and RY; Data analysis and interpretation were contributed by RY, SM and XZ; XL revised the manuscript and were the supporters of the study. All authors contributed to the article and approved the submitted version.
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Li, H., Ma, X., Yang, R. et al. Identification of ferroptosis-related proteins in ameloblastoma based on proteomics analysis. J Cancer Res Clin Oncol 149, 16717–16727 (2023). https://doi.org/10.1007/s00432-023-05412-8
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DOI: https://doi.org/10.1007/s00432-023-05412-8