Deregulation of desmosomal proteins and extracellular matrix proteases in odontogenic keratocyst

Objective: Odontogenic keratocyst (OKC) is a benign lesion that tends to recur after surgical treatment. In an attempt to clarify the molecular basis underlining the OKC pathobiology, we aimed to analyze its proteomic profile.

Materials and methods: We compared the proteomic profiles of five OKC and matched normal oral mucosa by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, we performed enrichment analysis and a literature search for the immunoexpression of the proteomics targets.

Results: We identified 1,150 proteins and 72 differently expressed proteins (log2 fold change ≥1.5; P < 0.05). Twenty-seven peptides were exclusively detected in the OKC samples. We found 35 enriched pathways related to cell differentiation and tissue architecture, including keratinocyte differentiation, keratinization, desmosome, and extracellular matrix (ECM) organization and degradation. The immunoexpression information of 11 out of 50 proteins identified in the enriched pathways was obtained. We found the downregulation of four desmosomal proteins (JUP, PKP1, PKP3, PPL) and upregulation of ECM proteases (MMP-2, MMP-9 and cathepsins).

Conclusions: Proteomic analysis strengthened the notion that OKC cells have a similar proteomic profile to oral keratinocytes. Contextual investigation of the differentially expressed proteins revealed the deregulation of desmosome proteins and ECM degradation as important alterations in OKC pathobiology.

Keywords: Cathepsins; Desmosomes; Matrix Metallopoteinases; Odontogenic Cysts; Odontogenic Tumor; Proteome.