Differentially expressed extracellular matrix genes functionally separate ameloblastoma from odontogenic keratocyst

Area of Science:

• Oncology
• Genomics
• Biochemistry

Background:

• Ameloblastoma and odontogenic keratocyst (OKC) are odontogenic tumors with invasive growth and high recurrence rates.
• While genetic mutations are known for both, distinct molecular indicators of ameloblastoma's aggressive characteristics remain unclear.
• Understanding these differences is crucial for targeted therapeutic strategies.

Purpose of the Study:

• To identify hub genes associated with ameloblastoma's growth characteristics using bioinformatic analysis.
• To compare gene expression profiles between ameloblastoma and OKC.
• To validate key gene expressions in clinical samples and xenografts.

Main Methods:

• RNA sequencing data from GSE186489 (GEO database) was analyzed using Galaxy and iDEP.
• Gene Ontology (GO) and pathway analysis were performed using ShineyGO.
• Protein-protein interaction (PPI) networks were constructed using STRING and visualized with Cytoscape to identify hub genes.
• Top hub genes (FN1, COL I, IGF-1) were validated via immunostaining in ameloblastoma, OKC, and mouse xenograft tissues.

Main Results:

• Seven hub genes were identified, with FN1, COL1A1/COL1A2, and IGF-1 linked to extracellular matrix organization and cell adhesion.
• Immunostaining confirmed FN1 and IGF-1 in ameloblastoma and OKC stroma, while COL 1 was only reactive in ameloblastoma.
• FN1 and IGF-1 expression levels were significantly lower in OKC compared to ameloblastoma.

Conclusions:

• This study validates the differential upregulation of matrix proteins FN1, COL I, and IGF-1 in ameloblastoma versus OKC.
• These findings suggest that distinct stromal architecture and growth characteristics in ameloblastoma may result from the interplay of these upregulated genes.
• The identified hub genes offer potential biomarkers for differentiating ameloblastoma from OKC.