RT Journal Article
T1 HMGA2 overexpression predicts relapse susceptibility of blastemal Wilms tumor patients
A1 Hontecillas-Prieto, Lourdes
A1 Garcia-Dominguez, Daniel J.
A1 Garcia-Mejias, Rosa
A1 Ramirez-Villar, Gema L.
A1 Saez, Carmen
A1 de Alava, Enrique
K1 Wilms tumors
K1 embryonic stem cell markers
K1 HMGA2
K1 blastemal stratification
K1 Embryonic stem-cells
K1 Childrens oncology group
K1 Gene-expression
K1 Mesenchymal transition
K1 International society
K1 Favorable histology
K1 Kidney development
K1 Signaling pathway
K1 Childhood-cancer
K1 Ovarian-cancer
AB Wilms tumor (WT) is an embryonal malignant neoplasm of the kidney that accounts for 6-7% of all childhood cancers. WT seems to derive from multipotent embryonic renal stem cells that have failed to differentiate properly. Since mechanisms underlying WT tumorigenesis remain largely unknown, the aim of this study was to explore the expression of embryonic stem cell (ESC) markers in samples of WT patients after chemotherapy treatment SIOP protocol, as the gene expression patterns of ESC are like those of most cancer cells. We found that expression of ESC markers is heterogeneous, and depends on histological WT components. Interestingly, among ESC markers, HMGA2 was expressed significantly stronger in the blastemal component than in the stromal and the normal kidney. Moreover, two subsets of patients of WT blastemal type were identified, depending on the expression levels of HMGA2. High HMGA2 expression levels were significantly associated with a higher proliferation rate (p=0.0345) and worse patient prognosis (p=0.0289). The expression of HMGA2 was a stage-independent factor of clinical outcome in blastemal WT patients. Our multivariate analyses demonstrated the association between LIN28B-LET7A-HMGA2 expression, and the positive correlation between HMGA2 and SLUG expression (p=0.0358) in blastemal WT components. In addition, patients with a poor prognosis and high HMGA2 expression presented high levels of MDR3 (multidrug resistance transporter). Our findings suggest that HMGA2 plays a prominent role in the pathogenesis of a subset of blastemal WT, strongly associated with relapse and resistance to chemotherapy.
PB Impact journals llc
YR 2017
FD 2017-12-29
LK http://hdl.handle.net/10668/19450
UL http://hdl.handle.net/10668/19450
LA en
DS RISalud
RD Apr 18, 2025