Differential Gene Expression and Pathway Analysis in Juvenile Nasopharyngeal Angiofibroma Using RNA Sequencing

Abstract

Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascularized and locally aggressive tumor that typically presents in adolescent males. The molecular biology of this tumor remains understudied. We sought to identify differentially expressed genes in the JNA transcriptome through messenger RNA sequencing of primary fibroblasts from 2 tumor explants and tonsil tissue from tumor-free subjects. In total, 1088 significant, differentially expressed genes were identified with 749 upregulated and 339 downregulated. Pathway analysis identified a number of activated signaling pathways, most notably, the vascular endothelial growth factor (VEGF) pathway (adjusted overlap P = .03). VEGF-A showed a 4.4-fold upregulation in JNA samples. In addition, the angiogenic receptor, fibroblast growth factor receptor 2 (FGFR2), was not present in tumor-free samples but increased in JNA. We validate these findings with immunohistochemistry, demonstrating upregulation of VEGF and FGFR2 in patient sections. Inhibition of the VEGF or FGFR signaling axes may have therapeutic potential in the treatment of JNA.

Experiencia en el tratamiento quirúrgico del angiofibroma nasal juvenil en Hospital de Especialidades No 2 Lic. Luis Donaldo Colosio Murrieta. Instituto Mexicano del Seguro Social de Ciudad Obregón, Sonora

“…Estudios hechos por Xiaole Song et al , mencionan a los niveles alto de HIF-1α (factor 1α inducible por hipoxia) en las células epiteliales de los tejidos JNA así como también CREG (represor celular de genes estimulados por E1A), OPN (osteopontina), c-Src (proto oncogene tirosinaproteína quinasa Src) y VEGF (facto vascular endotelial de crecimiento), como marcadores significativos de recurrencia y progresión del tumor. Otros autores como Joel W. Jones et al hacen referencia a la inhibición de los ejes de señalización de VEGF (factor vascular de crecimiento endotelial) y FGFR ( factor de crecimiento de fibroblastos) puede tener potencial terapéutico (22)(23)(24)(25)(26)(27) .…”

Master Regulators of Epithelial-Mesenchymal Transition and WNT Signaling Pathways in Juvenile Nasopharyngeal Angiofibromas

“…Since JNAs are highly vascularized, the search for deregulated pro-angiogenic growth factors has drawn particular attention. The overexpression of vascular endothelial growth factor A (VEGFA) has been consistently reported in several studies [ 8 , 9 , 10 , 11 ]. Although some studies detected VEGF primarily in endothelial cells, others reported its presence in stromal and endothelial cells, or even predominantly in stromal cells [ 12 ].…”

“…Although some studies detected VEGF primarily in endothelial cells, others reported its presence in stromal and endothelial cells, or even predominantly in stromal cells [ 12 ]. Increased expression levels of fibroblast growth factor (FGF) and fibroblast growth factor receptor (FGFR) have also been described in JNAs [ 8 , 10 , 11 , 13 ]. The FGF/FGFR signaling axis modulates mitosis and cell survival, differentiation, and migration [ 14 ].…”

“…The authors described that the WNT-activated receptor activity was enriched in high-stage tumors. RNA sequencing analysis was performed comparing primary fibroblasts from two JNA explants and tumor-free tonsil tissues, revealing 1088 DEGs [ 10 ]. Based on this result, an ingenuity pathway analysis (IPA) was carried out, predicting the activation of VEGF and FGFR signaling.…”

Neural Crest Stem Cells in Juvenile Angiofibromas

“…Pivotal studies in understanding JA's biology were descriptions of frequent β-catenin mutations; studies focusing on members of the Wnt-signalling pathway [3,4] as well as descriptions of genetic changes [5][6][7][8][9][10]. Further studies focused on angiogenesis or various growth factors as well as sex hormones and their receptors [1,[11][12][13][14] being involved in JA's.…”