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

Abstract

Objective. Ameloblastoma is a benign odontogenic tumor that may lead to ameloblastic carcinoma. is 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. e dataset GSE132472 was obtained from the GEO database, and multivariate statistical analyses were applied to identify di erentially 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. e Cytoscape software identi ed signi cant 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. Signi cant TFs and miRNAs acting on the hub genes were identi ed 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. e approved drugs acting on the hub genes were also found. Results. A total of 1,629 genes were di erentially 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 signi cant TF acting on the hub genes. BTK was the protein kinase signi cantly enriched by the TFs. Cholesterol biosynthesis was considerably involved in primary ameloblastoma. Conclusions. is study provides an intuition into the potential mechanisms involved in the etiology of ameloblastoma.

Photodynamic therapy with verteporfin accelerates apoptotic bleb formation in human ameloblastoma

“…The first is that higher expression of LDLR reflects the aggressiveness of tumor that require several surgeries. A previous database analysis indicated the possibility that cholesterol biosynthesis is involved in primary ameloblastoma (Bayat et al., 2022). Recently, the overexpression of LDLR has been found in various cancers, because cancer cells require more cholesterol to obtain energy than normal cells (Deng et al., 2022).…”

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach

“…The single proteins were excluded from the primary PIM before further analysis. The PIM was analyzed using the Cytoscape software [ 77 ], leading to the identification of hub genes with the highest degree and betweenness centralities [ 78 ]. Moreover, clustering analysis was performed using the MCODE tool.…”

MicroRNA-Based Markers of Oral Tongue Squamous Cell Carcinoma and Buccal Squamous Cell Carcinoma: A Systems Biology Approach

“…Possible interactions among the targets with a combined score of 0.4 [ 29 ] were indicated using the STRING knowledge tool, available at http://string-db.org/ [ 30 ]. After removing disconnected nodes inside the protein interaction map (PIM) [ 31 ], the connected network was downloaded as a TSV format and subsequently imported into the Cytoscape 3.9.1 software [ 32 ], available at https://www.cytoscape.org to perform structural analysis. Hub nodes were awarded to proteins whose degree and betweenness were above two times the average and whose closeness exceeded the mean of the PPI network's nodes.…”