FXR1 expression domain in Wilms tumor.
Embryonal tumor
FXR1
Nephroblastoma
Pediatric cancer
Wilms tumor
Journal
Journal of pediatric surgery
ISSN: 1531-5037
Titre abrégé: J Pediatr Surg
Pays: United States
ID NLM: 0052631
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
12
02
2019
accepted:
21
02
2019
pubmed:
22
3
2019
medline:
27
8
2019
entrez:
22
3
2019
Statut:
ppublish
Résumé
Wilms tumor (WT) is the most common childhood kidney cancer globally. Our prior unbiased proteomic screen of WT disparities revealed increased expression of Fragile X-Related 1 (FXR1) in Kenyan specimens where survival is dismal. FXR1 is an RNA-binding protein that associates with poor outcomes in multiple adult cancers. The aim of this study therefore was to validate and characterize the FXR1 expression domain in WT. Quantitative FXR1 gene expression was compared between WT, adjacent, adult, and fetal kidney specimens. The cellular and subcellular expression domain of FXR1 was characterized across these tissues using immunoperoxidase staining. RNA-sequencing of FXR1 was performed from WT and other pediatric malignancies to examine its broader target potential. FXR1 was detected in all clinical WT specimens evaluated (n = 82), and as a result appeared independent of demographic, histology, or adverse event. Specific cytosolic staining was strongest in blastema, intermediate and variable in epithelia, and weakest in stroma. When present, areas of skeletal muscle differentiation stained strongly for FXR1. qPCR revealed increased FXR1 expression in WT compared to adult and adjacent kidney (p < 0.0002) but was similar to fetal kidney (p = 0.648). RNA-sequencing revealed expression of FXR1 in multiple pediatric tumors, greatest in rhabdomyosarcoma and WT. FXR1 was expressed consistently across this broad sampling of WT and most robustly in the primitive blastema. Notably, FXR1 labeled a specific self-renewing progenitor population of the fetal kidney.
Sections du résumé
BACKGROUND/PURPOSE
OBJECTIVE
Wilms tumor (WT) is the most common childhood kidney cancer globally. Our prior unbiased proteomic screen of WT disparities revealed increased expression of Fragile X-Related 1 (FXR1) in Kenyan specimens where survival is dismal. FXR1 is an RNA-binding protein that associates with poor outcomes in multiple adult cancers. The aim of this study therefore was to validate and characterize the FXR1 expression domain in WT.
METHODS
METHODS
Quantitative FXR1 gene expression was compared between WT, adjacent, adult, and fetal kidney specimens. The cellular and subcellular expression domain of FXR1 was characterized across these tissues using immunoperoxidase staining. RNA-sequencing of FXR1 was performed from WT and other pediatric malignancies to examine its broader target potential.
RESULTS
RESULTS
FXR1 was detected in all clinical WT specimens evaluated (n = 82), and as a result appeared independent of demographic, histology, or adverse event. Specific cytosolic staining was strongest in blastema, intermediate and variable in epithelia, and weakest in stroma. When present, areas of skeletal muscle differentiation stained strongly for FXR1. qPCR revealed increased FXR1 expression in WT compared to adult and adjacent kidney (p < 0.0002) but was similar to fetal kidney (p = 0.648). RNA-sequencing revealed expression of FXR1 in multiple pediatric tumors, greatest in rhabdomyosarcoma and WT.
CONCLUSIONS
CONCLUSIONS
FXR1 was expressed consistently across this broad sampling of WT and most robustly in the primitive blastema. Notably, FXR1 labeled a specific self-renewing progenitor population of the fetal kidney.
Identifiants
pubmed: 30894247
pii: S0022-3468(19)30171-X
doi: 10.1016/j.jpedsurg.2019.02.030
pmc: PMC6545243
mid: NIHMS1524314
pii:
doi:
Substances chimiques
FXR1 protein, human
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Pagination
1198-1205Subventions
Organisme : NCI NIH HHS
ID : R01 CA102353
Pays : United States
Organisme : NIH HHS
ID : S10 OD016355
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA152662
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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