Study of transcriptome (Seq RNA) and miRNoma (Small RNA Seq) in non-small cell lung cancer for the study of intratumoral heterogeneity. Finding molecular markers prognostic and extreme sensitivity to treatment (Q3164239)

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Project Q3164239 in Spain
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Study of transcriptome (Seq RNA) and miRNoma (Small RNA Seq) in non-small cell lung cancer for the study of intratumoral heterogeneity. Finding molecular markers prognostic and extreme sensitivity to treatment
Project Q3164239 in Spain

    Statements

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    51,000.0 Euro
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    102,000.0 Euro
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    50.0 percent
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    1 January 2015
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    31 March 2018
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    FUNDACION CENTRO NAL DE INV. CARDIOVASCULARES CARLOS III
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    40°25'0.12"N, 3°42'12.89"W
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    28079
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    El cáncer de pulmón es uno de los de mayor tasa de mortalidad a nivel mundial, y el de tipo no microcítico (CPNM) el más frecuente y de difícil tratamiento. En CPNM, aunque el fracaso en la aplicación clínica de los datos moleculares está vinculado a multitud de factores, la heterogeneidad intratumoral se cree que juega un papel clave. Se piensa que la heterogeneidad de un tumor tipo CPNM es debida a la capacidad de las células iniciadoras tumorales (CIT) de autorenovarse y de diferenciar en diferentes tipos de células tumorales, y que esto viene regulado por el microambiente tumoral. En el presente subproyecto planteamos determinar el impacto de diferentes componentes del microambiente tumoral de CPNM sobre el programa transcripcional de las CIT. A partir de muestras clínicas de pacientes se purificaran las CIT y se cocultivaran con diferentes componentes celulares de su microentorno. Mediante la secuenciación del transcriptoma (RNA-Seq) y del miRNoma (Small-RNASeq) de estas CITs determinaremos la contribución específica de diferentes componentes del microambiente en la autorenovación, proliferación y diferenciación de estas células clave para la formación, progresión y resistencia del CPNM. Este tipo de caracterización molecular podría resultar en la identificación nuevos biomarcadores de progresión o en dianas antitumorales. También caracterizaremos la transcriptómica (single-cell RNA Seq) de células tumorales circulantes que se encuentran en la sangre de pacientes en estadios avanzados. Se pretende así investigar cambios transcripcionales que arrojen luz sobre el proceso de metástasis y que abran nuevos caminos para combatirlo (Spanish)
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    Lung cancer is one of the highest mortality rates worldwide, and non-small cell cancer (NCP) is the most frequent and difficult to treat. In NSCLC, although failure in the clinical application of molecular data is linked to a multitude of factors, intratumoral heterogeneity is believed to play a key role. The heterogeneity of a NSCLC-type tumor is thought to be due to the ability of tumor initiating cells (ITC) to self-renovate and to differentiate into different types of tumor cells, and that this is regulated by the tumor microenvironment. In this sub-project we propose to determine the impact of different components of the NSCLC tumor microenvironment on the ILC transcriptional program. From clinical samples of patients, CITs will be purified and cocultivated with different cellular components of their microenvironment. By sequencing the transcriptome (RNA-Seq) and miRNoma (Small-RNASeq) of these CITs we will determine the specific contribution of different components of the microenvironment in the self-renewal, proliferation and differentiation of these key cells for the formation, progression and resistance of NSCLC. This type of molecular characterisation could result in the identification of new progression biomarkers or antitumor targets. We will also characterise the transcriptomic (single-cell RNA Seq) of circulating tumor cells found in the blood of advanced-stage patients. It is intended to investigate transcriptional changes that shed light on the process of metastasis and open new ways to combat it. (English)
    12 October 2021
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    Madrid
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    Identifiers

    PI14_02120
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