Abstract
Juvenile nasopharyngeal angiofibroma (JNA) is a rare fibrovascular benign tumor showing an invasive growth pattern and affecting mainly male adolescents. We investigated the role of epithelial–mesenchymal transition (EMT) and WNT signaling pathways in JNA. Gene expression profiles using nine JNA paired with four inferior nasal turbinate samples were interrogated using a customized 2.3K microarray platform containing genes mainly involved in EMT and WNT/PI3K pathways. The expression of selected genes (BCL2, CAV1, CD74, COL4A2, FZD7, ING1, LAMB1, and RAC2) and proteins (BCL2, CAV1, CD74, FZD7, RAF1, WNT5A, and WNT5B) was investigated by RT-qPCR (28 cases) and immunohistochemistry (40 cases), respectively. Among 104 differentially expressed genes, we found a significantly increased expression of COL4A2 and LAMB1 and a decreased expression of BCL2 and RAC2 by RT-qPCR. The immunohistochemistry analysis revealed a low expression of BCL2 and a negative to moderate expression of FZD7 in most samples, while increased CAV1 and RAF1 expression were detected. Moderate to strong CD74 protein expression was observed in endothelial and inflammatory cells. A significant number of JNAs (78%) presented reduced WNT5A and increased WNT5B expression. Overall, the transcript and protein profile indicated the involvement of EMT and WNT pathways in JNA. These candidates are promising druggable targets for treating JNA.
Highlights
Juvenile nasopharyngeal angiofibroma (JNA) is a benign mesenchymal neoplasm characterized by a high vessel density that occurs almost exclusively in male adolescents and young adults
The 2.3K microarray platform used for large-scale expression analysis included cancer-related genes, such as those involved in the WNT/PI3K pathway and epithelial–mesenchymal transition (EMT) process
The top 10 biological processes and pathways enriched in JNAs, according to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), NCINature, and BioCarta gene-set libraries, obtained with the Enrichr tool, are presented in JNA-related pathways (Figure 2A)
Summary
Juvenile nasopharyngeal angiofibroma (JNA) is a benign mesenchymal neoplasm characterized by a high vessel density that occurs almost exclusively in male adolescents and young adults. Imaging analyses have demonstrated that the tumor arises from the choana region and nasopharynx [1]. JNA presents a locally infiltrative growth pattern that often displays skull base invasion at diagnosis and less commonly spreads through the orbital fissure, resulting in an intracranial extension [2]. Whereas the etiopathogenesis of these tumors remains elusive, there is evidence suggesting the potential influence of sex hormones and genetic factors, including familial adenomatous polyposis [4,5]. In a limited number of cases, the upregulation of pro-angiogenic growth factors and infection with human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV) have been described [5,6,7]
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