Translational study of Hepatoblastoma: from integral omic analysis to the identification, validation and therapeutic application of prognostic biomarkers for incorporation into clinical practice. (Q3155151)

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Project Q3155151 in Spain
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English
Translational study of Hepatoblastoma: from integral omic analysis to the identification, validation and therapeutic application of prognostic biomarkers for incorporation into clinical practice.
Project Q3155151 in Spain

    Statements

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    33,125.0 Euro
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    66,250.0 Euro
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    50.0 percent
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    1 January 2014
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    31 March 2017
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    FUNDACION INSTITUTO DE INVESTIGACION EN CIENCIAS DE LA SALUD GERMANS TRIAS I PUJOL
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    41°26'57.66"N, 2°14'53.70"E
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    08015
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    El Hepatoblastoma (HB) es el principal tumor maligno del hígado en la infancia. El tratamiento curativo se consigue combinando quimioterapia y cirugía. No obstante, un 20% de los niños no sobreviven a la enfermedad y los que sobreviven pueden sufrir secuelas graves de por vida. El presente proyecto tiene como objetivo (i) caracterizar e identificar nuevos marcadores pronóstico de las formas más agresivas de HB a partir de un estudio molecular integral transcriptómico, genómico y proteómico, (ii) generar un conjunto altamente validado de biomarcadores y (iii) evaluar su valor teranóstico, con el objetivo global de mejorar el manejo clínico y la supervivencia de los pacientes con HB. En consecuencia, hemos creado una de las mayores colecciones mundiales de muestras de HB, que incluye formas muy agresivas y poco estudiadas. La caracterización de estos tumores se realizará a nivel transcriptómico (RNA-Seq) y genómico (Exome sequencing y arrays de SNP). Los datos generados se integrarán con datos clínicos, proteómicos y de expresión génica obtenidos previamente, utilizando distintos programas bioinformáticos. La validación de los biomarcadores se realizará mediante qPCR, secuenciación, inmunohistoquímica y FISH en >200 HBs. Finalmente, la utilidad terapéutica de determinados biomarcadores se estudiará en xenografts establecidos a partir de HB humano y líneas celulares derivadas de los mismos. Este es un estudio altamente traslacional, puesto que los resultados obtenidos se incluirán en próximos ensayos clínicos dirigidos por el grupo internacional SIOPEL (Childhood Liver Tumours Strategy Group). Además, aunque el HB sea un tumor raro, datos previos indican que los resultados podrían ser extrapolables a otros cánceres más frecuentes, como el hepatocarcinoma. (Spanish)
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    Hepatoblastoma (HB) is the main malignant tumor of the liver in childhood. Curative treatment is achieved by combining chemotherapy and surgery. However, 20 per cent of children do not survive the disease and those who survive may suffer severe lifetime sequelae. The objective of this project is (i) to characterise and identify new prognostic markers of the most aggressive forms of BH from an integral transcriptonomic, genomic and proteomic molecular study, (ii) to generate a highly validated set of biomarkers and (iii) to evaluate their theoretical value, with the overall objective of improving the clinical management and survival of patients with BH. As a result, we have created one of the world’s largest collections of HB samples, which includes very aggressive and poorly studied forms. The characterisation of these tumors will be performed at the transcriptomic (RNA-Seq) and genomic level (Exome sequencing and SNP arrays). The data generated will be integrated with previously obtained clinical, proteomic and gene expression data, using different bioinformatics programs. Biomarker validation shall be performed by qPCR, sequencing, immunohistochemistry and FISH at >200 HBs. Finally, the therapeutic usefulness of certain biomarkers will be studied in xenografts established from human HB and cell lines derived from them. This is a highly translational study, as the results obtained will be included in upcoming clinical trials led by the international SIOPEL group (Childhood Liver Tumours Strategy Group). In addition, although HB is a rare tumor, previous data indicate that the results may be extrapolated to other more frequent cancers, such as hepatocarcinoma. (English)
    12 October 2021
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    Badalona
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    Identifiers

    PI13_02340
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