Proteomics profiling of keratocystic odontogenic tumours reveals <scp>AIDA</scp> as novel biomarker candidate

Malčić, Ana Ivanišević; Breen, Lucas; Josić, Djuro; Krmek, Silvana Jukić; Džombeta, Tihana; Matijević, Jurica; Grgurević, Lovro; Pavelić, Krešimir; Krušlin, Božo; Pavelić, Sandra Kraljević

doi:10.1111/jop.12239

Cited by 4 publications

(3 citation statements)

References 39 publications

(41 reference statements)

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“…In the present study, we investigated the proteomic profile of OKC using LC‐MS/MS method. In 2015, Malčić et al reported a comparative proteomic profiling of OKC, oral mucosa, and radicular cyst using LC‐MS/MS, but focusing on identifying potential biomarkers (Ivanišević Malčić et al., 2015). Fold‐calculation and downregulated proteins were not provided.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of desmosomal proteins and extracellular matrix proteases in odontogenic keratocyst

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Deregulation of desmosomal proteins and extracellular matrix proteases in odontogenic keratocyst

et al. 2020

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“…In addition to these studies, which have focused on specific genomic regions, genes or proteins, a few investigations have evaluated global molecular changes in OKCs. An analysis of OKC proteomics was carried out by comparing OKC lesions with patient‐matched normal oral mucosa . This study revealed 43 differentially expressed proteins in OKCs, including proteins involved in the JNK and p38 MAPK signaling pathways …”

Section: Genetic Alterationsmentioning

confidence: 99%

“…An analysis of OKC proteomics was carried out by comparing OKC lesions with patient‐matched normal oral mucosa . This study revealed 43 differentially expressed proteins in OKCs, including proteins involved in the JNK and p38 MAPK signaling pathways …”

Section: Genetic Alterationsmentioning

confidence: 99%

Molecular alterations in odontogenic keratocysts as potential therapeutic targets

Gomes

Guimarães

Diniz

et al. 2017

J Oral Pathology Medicine

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The odontogenic keratocyst (OKC) is a cystic lesion, lined by uniformly thickened parakeratinized epithelium. Some lesions are large and tend to recur after surgical treatment. The neoplastic nature of OKCs remains a matter of dispute. It is known that some sporadic OKCs harbor PTCH1 mutations, and via the dissection of cyst epithelium, these mutations were demonstrated to occur much more frequently than previously thought. In addition to the classical PTCH1 mutations, Hedgehog pathway disturbance and Bcl-2 protein overexpression, as detected via genome-wide expression analysis of OKCs, have been published. Changes in DNA methylation patterns and alterations in microRNA expression levels have recently been reported in these lesions. We reviewed the molecular mechanisms that underlie the pathogenesis of OKCs as described over the past few years and explored the molecular alterations that can be therapeutically targeted.

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New diagnostic molecular markers and biomarkers in odontogenic tumors

et al. 2021

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Odontogenic tumors comprised of complex heterogeneous lesions that diverse from harmatomas to malignant tumors with different behavior and histology. The etiology of odontogenic tumors is not exactly determined and pathologists deal with challenges in diagnosis of odontogenic tumors because they are rare and obtained experiences are difficult to evaluate. In this study, we describe immunohistochemical and molecular markers in diagnosis of odontogenic tumors besides advanced diagnostic technique. Immunohistochemical features of odontogenic tumors beside the clinical features and radiological finding can help us to determine the correct diagnosis. Although these markers are neither specific nor sensitive enough, but analysis of gene expression provides definitive confirmation of diagnosis. In addition, “-omics” technology detected specific molecular alternation associated with etiology such as genomics, epigenomics, transcriptomics, proteomics and metabolomics. The post transcriptional events such as DNA methylation and chromatin remodeling by histone modification affect the changes in epigenome. Furthermore, non-coding RNAs like micro-RNAs, long noncoding RNA (lncRNA) and small non-coding RNA (snoRNA) play regulatory role and impact odontogenesis. Molecular marker propose their potential role in etiopathogenesis of odontogenic tumors and suitable candidate in diagnostic, prognostic and therapeutic approaches in addition to patient management. For future evaluations, organoid represents in vitro tumor model-study for tumor behavior, metastasis and invasion, drug screening, immunotherapy, clinical trial, hallmarks association with prognosis and evolution of personalized anti-cancer therapy. Moreover, organoid biobank help us to check genetic profile. We think more investigation and studies are needed to gain these knowledges that can shift therapeutic approaches to target therapy.

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Proteomics profiling of keratocystic odontogenic tumours reveals AIDA as novel biomarker candidate

Cited by 4 publications

References 39 publications

Deregulation of desmosomal proteins and extracellular matrix proteases in odontogenic keratocyst

Deregulation of desmosomal proteins and extracellular matrix proteases in odontogenic keratocyst

Molecular alterations in odontogenic keratocysts as potential therapeutic targets

New diagnostic molecular markers and biomarkers in odontogenic tumors

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