Deregulation of desmosomal proteins and extracellular matrix proteases in odontogenic keratocyst

Abstract

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 < .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, and 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.

Decoding a gene expression program that accompanies the phenotype of sporadic and basal cell nevus syndrome‐associated odontogenic keratocyst

“…Our analysis revealed that sporadic and BCNS‐associated OKCs share a significantly common (85%) transcriptomics profile when compared with the DF. This is consistent with the results of our recent systematic review on the immunohistochemical profile of OKCs, 27 a study on the protein expression profile of OKC cell lines, 28 as well as an elegant proteomics study employing four sporadic and one BCNS‐associated OKCs, where no significant differences were found between the two subtypes 29 . Our data support the notion that sporadic and BCNS‐associated OKCs may share the same cell origin and their pathogenesis might be driven by common molecular mechanism(s) 1,28 .…”

“…This is consistent with the results of our recent systematic review on the immunohistochemical profile of OKCs, 27 a study on the protein expression profile of OKC cell lines, 28 as well as an elegant proteomics study employing four sporadic and one BCNS-associated OKCs, where no significant differences were found between the two subtypes. 29 Our data support the notion that sporadic and BCNS-associated OKCs may share the same cell origin and their pathogenesis might be driven by common molecular mechanism(s). 1,28 Finally, we observed a highly (80.5%) shared gene expression profile among primary and recurrent sporadic OKCs, and, thus, processed them as one group, in line with previous studies.…”

Proteomic Analysis Revealed Different Molecular Mechanisms of Response to PEG Stress in Drought-Sensitive and Drought-Resistant Sorghums

“…In order to identify DAPs observed in S4, S4-1, T14, and T33 sorghum varieties under drought stress compared with the control group, the p -value < 0.05 and up/downregulation with ± 1.5 FC was used as the filter criterion [ 19 ]. A total of 46 (14 consensus/32 PEG S4 unique proteins), 36 (7 consensus/13 S4-1 unique/16 PEG S4-1 unique proteins), 35 (8 consensus/13 T14 unique/14 PEG T14 unique proteins), and 102 (37 consensus/38 T33 unique/27 PEG T33 unique proteins) DAPs were identified, of which 46, 20, 21, and 48 DAPs were upregulated and 0, 16, 14, and 54 DAPs were downregulated, respectively ( Table S5 ).…”

Unveiling metabolic changes in marsupialized odontogenic keratocyst: A pilot study

“…Galactose metabolism has been associated with detachment and differentiation of keratinocytes in a cell culture model (Banno & Blumenberg, 2014). The detachment of keratinocytes in OKC is suggested to be a product of an impaired desmosomal protein complex (Diniz et al., 2020). Consistently, our analysis revealed significantly altered regulation of galactose metabolism in OKC before marsupialization.…”

“…Corroborating this finding, we observed altered regulation of glycolysis and gluconeogenesis in our metabolomic analysis, which can be related to OKC development. Carnitine can also be associated with this context since it acts like a “shuttle‐molecule” that promotes mitochondrial fatty acid oxidation, which serves as (Diniz et al., 2020) a powerful energy substrate for cell growth (Console et al., 2020).…”