HMGA2 overexpression predicts relapse susceptibility of blastemal Wilms tumor patients
| Autor: | Gema L. Ramírez-Villar, Lourdes Hontecillas-Prieto, Daniel J. García-Domínguez, Carmen Sáez, de Álava E, Rosa Garcia-Mejias |
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| Přispěvatelé: | Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Andalucía, Ministerio de Economía y Competitividad (España), European Commission, Instituto de Salud Carlos III, [Hontecillas-Prieto, Lourdes] Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville IBiS, Pathol Unit,CSIC,CIBERONC, Seville, Spain, [Garcia-Dominguez, Daniel J.] Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville IBiS, Pathol Unit,CSIC,CIBERONC, Seville, Spain, [Garcia-Mejias, Rosa] Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville IBiS, Pathol Unit,CSIC,CIBERONC, Seville, Spain, [Saez, Carmen] Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville IBiS, Pathol Unit,CSIC,CIBERONC, Seville, Spain, [de Alava, Enrique] Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville IBiS, Pathol Unit,CSIC,CIBERONC, Seville, Spain, [Ramirez-Villar, Gema L.] Univ Seville, Hosp Univ Virgen del Rocio, CSIC, Pediat Oncol Unit, Seville, Spain, Red Tematica de Investigacion Cooperativa en Cancer, Nicolas Monardes Program, Consejeria de Salud, Junta de Andalucia, Ministry of Economy and Competitiveness of Spain-FEDER (CIBERONC, FMGE), Consejeria de Salud, Junta de Andalucia, Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica |
| Rok vydání: | 2017 |
| Předmět: |
Childhood-cancer
0301 basic medicine Oncology medicine.medical_specialty HMGA2 Stromal cell Kidney development medicine.medical_treatment Ovarian-cancer medicine.disease_cause Wilms tumors Favorable histology 03 medical and health sciences blastemal stratification 0302 clinical medicine embryonic stem cell markers Internal medicine Embryonic stem cell markers medicine Gene-expression Renal stem cell Blastemal stratification Chemotherapy biology Signaling pathway business.industry Wilms' tumor Embryonic stem-cells International society medicine.disease Embryonic stem cell 3. Good health 030104 developmental biology Mesenchymal transition 030220 oncology & carcinogenesis Cancer cell biology.protein Childrens oncology group Carcinogenesis business Research Paper |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname idUS. Depósito de Investigación de la Universidad de Sevilla idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. LHP and DJGD are supported by Red Temática de Investigación Cooperativa en Cáncer (RD12/0036/0017). CS is supported by a contract from Nicolás Monardes Program, Consejería de Salud, Junta de Andalucía. Research in Enrique de Alava’s lab is supported by the Ministry of Economy and Competitiveness of Spain-FEDER (CIBERONC, PI1700464, RD06/0020/0059, FMGE) and the European Commission (FP7-HEALTH-2011-two-stage, Project ID 278742 EUROSARC). DJGD is a PhD researcher funded by the Consejería de Salud, Junta de Andalucía (PI-0197-2016). Research in Carmen Sáez’s lab is also supported by research grants from the Instituto de Salud Carlos III, FIS PI13/02282. |
| Databáze: | OpenAIRE |
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