Publication: Diagnóstico y pronóstico del cáncer colorrectal mediante la cuantificación de anticuerpos en suero de pacientes
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2018-08-23
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Universidad Complutense de Madrid
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Abstract
Los estudios de esta Tesis Doctoral se realizaron en el Centro de Investigaciones Biológicas (CIB-CSIC) y pretenden continuar el análisis de la respuesta humoral inmune en cáncer colorrectal (CCR) iniciado en el Laboratorio de Proteómica Funcional desde una perspectiva traslacional. El cáncer colorrectal (CCR) es el cáncer de mayor mortalidad en los países desarrollados. Por tanto, el CCR supone un serio problema de salud que requiere mejoras en el diagnóstico temprano de la enfermedad y un pronóstico más preciso de la evolución del paciente. La respuesta inmunológica humoral que desarrollan los pacientes con cáncer frente a proteínas alteradas durante la formación y progresión tumoral ofrece una serie de biomarcadores que podrían ayudar a mejorar la supervivencia de la enfermedad al permitir un diagnóstico temprano de la patología y mejorar el manejo del paciente ya diagnosticado. Los autoanticuerpos son marcadores circulantes que suponen una nueva herramienta para el cribado poblacional al satisfacer un alto grado de precisión, no invasividad, reproducibilidad y suponer una oportunidad de ahorro debido al bajo coste de su detección. El objetivo final de la Tesis Doctoral fue obtener un panel de autoantígenos asociados a tumor (AAT) específicos de CCR útil para el diagnóstico y pronóstico de los pacientes de la enfermedad. Para ello, partimos de un panel de AAT descubiertos a través de micromatrices de proteínas utilizando un reducido número de muestras. Durante la Tesis Doctoral, se optimizó la expresión recombinante de los antígenos previamente descubiertos y se desarrolló y validó un método de detección múltiple de autoanticuerpos mediante Luminex, comparando los datos obtenidos mediante ELISA...
Colorectal cancer (CRC) is the leading cause of cancer associated death in developed countries. Therefore, CRC has become a major public health problem in which current techniques of secondary and tertiary prevention are not enough to manage the disease. The humoral immune developed by cancer patients provides autoantibodies as biomarkers, which could help to improve patients’ survival allowing for an early diagnosis of the disease and a better management of diagnosed patients. Autoantibodies directed to altered proteins during the formation and progression of colorectal cancer are circulating markers, which could be used for CRC population screening, satisfying a high degree of accuracy, non-invasiveness, reproducibility and low cost. In addition, autoantibody detection is easily implementable to a clinical routine, as antibodies are well characterized molecules and immunoassays are techniques already used in research and clinical diagnosis of different diseases. Here presented studies were conducted at the Center for Biological Research (CIB-CSIC) and intended to continue the analysis of the humoral immune response in CRC initiated in the Functional Proteomics Laboratory but from a translational perspective. To that end, we started from a panel of tumor-associated autoantigens (TAA) discovered through the screening of protein microarrays to demonstrate the utility of CRC autoantibodies for the diagnosis of the disease and with the ultimate goal of obtaining a panel of CRCspecific TAA useful for diagnosis and prognosis of patients using for a such a puropose both, murine models of CRC and human samples from CRC patients and controls, respectively. Thus, to demonstrate the utility of the autoantibodies for the early CRC diagnosis, we have studied the humoral immune response to CRC in chemically induced murine models of colorectal cancer. Therefore, we demonstrated that CRC murine models reproduced the human humoral immune response to the same TAA than in human. Autoantibodies directed against CRC-specific TAA were detected in early stages of the disease and, in general, increased in parallel to the tumor progression, demonstrating the enormous diagnostic potential of autoantibodies. In this study, we could also describe the molecular alterations that result in immune responses in cancer, finding that TAA overexpression is an important event in the formation of autoantibodies...
Colorectal cancer (CRC) is the leading cause of cancer associated death in developed countries. Therefore, CRC has become a major public health problem in which current techniques of secondary and tertiary prevention are not enough to manage the disease. The humoral immune developed by cancer patients provides autoantibodies as biomarkers, which could help to improve patients’ survival allowing for an early diagnosis of the disease and a better management of diagnosed patients. Autoantibodies directed to altered proteins during the formation and progression of colorectal cancer are circulating markers, which could be used for CRC population screening, satisfying a high degree of accuracy, non-invasiveness, reproducibility and low cost. In addition, autoantibody detection is easily implementable to a clinical routine, as antibodies are well characterized molecules and immunoassays are techniques already used in research and clinical diagnosis of different diseases. Here presented studies were conducted at the Center for Biological Research (CIB-CSIC) and intended to continue the analysis of the humoral immune response in CRC initiated in the Functional Proteomics Laboratory but from a translational perspective. To that end, we started from a panel of tumor-associated autoantigens (TAA) discovered through the screening of protein microarrays to demonstrate the utility of CRC autoantibodies for the diagnosis of the disease and with the ultimate goal of obtaining a panel of CRCspecific TAA useful for diagnosis and prognosis of patients using for a such a puropose both, murine models of CRC and human samples from CRC patients and controls, respectively. Thus, to demonstrate the utility of the autoantibodies for the early CRC diagnosis, we have studied the humoral immune response to CRC in chemically induced murine models of colorectal cancer. Therefore, we demonstrated that CRC murine models reproduced the human humoral immune response to the same TAA than in human. Autoantibodies directed against CRC-specific TAA were detected in early stages of the disease and, in general, increased in parallel to the tumor progression, demonstrating the enormous diagnostic potential of autoantibodies. In this study, we could also describe the molecular alterations that result in immune responses in cancer, finding that TAA overexpression is an important event in the formation of autoantibodies...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular, leída el 05-05-2017