Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Objective. Ameloblastoma is a benign odontogenic tumor that may lead to ameloblastic carcinoma. This study aimed to determine potential signaling pathways and biological processes, critical genes and their regulating transcription factors (TFs), and miRNAs, as well as protein kinases involved in the...

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Main Authors: Zeynab Bayat, Azin Mirzaeian, Amir Taherkhani
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:International Journal of Dentistry
Online Access:http://dx.doi.org/10.1155/2022/3316313
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author Zeynab Bayat
Azin Mirzaeian
Amir Taherkhani
author_facet Zeynab Bayat
Azin Mirzaeian
Amir Taherkhani
author_sort Zeynab Bayat
collection DOAJ
description Objective. Ameloblastoma is a benign odontogenic tumor that may lead to ameloblastic carcinoma. This study aimed to determine potential signaling pathways and biological processes, critical genes and their regulating transcription factors (TFs), and miRNAs, as well as protein kinases involved in the etiology of primary ameloblastoma. Methods. The dataset GSE132472 was obtained from the GEO database, and multivariate statistical analyses were applied to identify differentially expressed genes (DEGs) in primary ameloblastoma tissues compared to the corresponding normal gingiva samples. A protein-protein interaction (PPI) map was built using the STRING database. The Cytoscape software identified significant modules and the hub genes within the PPI network. Gene Ontology annotation and signaling pathway analyses were executed by employing the DAVID and Reactome databases, respectively. Significant TFs and miRNAs acting on the hub genes were identified using the iRegulon plugin and MiRWalk 2.0 database, respectively. A protein kinase enrichment analysis was conducted using the online Kinase Enrichment Analysis 2 (KEA2) web server. The approved drugs acting on the hub genes were also found. Results. A total of 1,629 genes were differentially expressed in primary ameloblastoma (P value <0.01 and |Log2FC| > 1). HRAS, CDK1, MAPK3, ERBB2, COL1A1, CYCS, and BRCA1 demonstrated high degree and betweenness centralities in the PPI network. E2F4 was the most significant TF acting on the hub genes. BTK was the protein kinase significantly enriched by the TFs. Cholesterol biosynthesis was considerably involved in primary ameloblastoma. Conclusions. This study provides an intuition into the potential mechanisms involved in the etiology of ameloblastoma.
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spelling doaj-art-976a0df3c4fd4b8894e6d3f9c220cfe32025-02-03T01:20:06ZengWileyInternational Journal of Dentistry1687-87362022-01-01202210.1155/2022/3316313Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology ApproachZeynab Bayat0Azin Mirzaeian1Amir Taherkhani2Department of Oral and Maxillofacial MedicineDepartment of Oral and Maxillofacial MedicineResearch Center for Molecular MedicineObjective. Ameloblastoma is a benign odontogenic tumor that may lead to ameloblastic carcinoma. This study aimed to determine potential signaling pathways and biological processes, critical genes and their regulating transcription factors (TFs), and miRNAs, as well as protein kinases involved in the etiology of primary ameloblastoma. Methods. The dataset GSE132472 was obtained from the GEO database, and multivariate statistical analyses were applied to identify differentially expressed genes (DEGs) in primary ameloblastoma tissues compared to the corresponding normal gingiva samples. A protein-protein interaction (PPI) map was built using the STRING database. The Cytoscape software identified significant modules and the hub genes within the PPI network. Gene Ontology annotation and signaling pathway analyses were executed by employing the DAVID and Reactome databases, respectively. Significant TFs and miRNAs acting on the hub genes were identified using the iRegulon plugin and MiRWalk 2.0 database, respectively. A protein kinase enrichment analysis was conducted using the online Kinase Enrichment Analysis 2 (KEA2) web server. The approved drugs acting on the hub genes were also found. Results. A total of 1,629 genes were differentially expressed in primary ameloblastoma (P value <0.01 and |Log2FC| > 1). HRAS, CDK1, MAPK3, ERBB2, COL1A1, CYCS, and BRCA1 demonstrated high degree and betweenness centralities in the PPI network. E2F4 was the most significant TF acting on the hub genes. BTK was the protein kinase significantly enriched by the TFs. Cholesterol biosynthesis was considerably involved in primary ameloblastoma. Conclusions. This study provides an intuition into the potential mechanisms involved in the etiology of ameloblastoma.http://dx.doi.org/10.1155/2022/3316313
spellingShingle Zeynab Bayat
Azin Mirzaeian
Amir Taherkhani
Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach
International Journal of Dentistry
title Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach
title_full Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach
title_fullStr Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach
title_full_unstemmed Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach
title_short Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach
title_sort potential biomarkers and signaling pathways associated with the pathogenesis of primary ameloblastoma a systems biology approach
url http://dx.doi.org/10.1155/2022/3316313
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AT amirtaherkhani potentialbiomarkersandsignalingpathwaysassociatedwiththepathogenesisofprimaryameloblastomaasystemsbiologyapproach