New tumour markers for pancreatic cancer based on the altered glycosylation of serum glycoproteins

Pancreatic cancer (PaC) is the deadliest of all tumours, with a 5-year survival below 12% and a mortality/incidence ratio of 94.5%. One of the main reasons behind this dismal prognosis is the diagnosis of the disease at late stages, usually when metastasis have already occurred and no effective ther...

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Detalles Bibliográficos
Autor: Duran Sidera, Adrià
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/690140
Acceso en línea:http://hdl.handle.net/10803/690140
Access Level:acceso abierto
Palabra clave:Càncer de pàncrees
Cáncer de páncreas
Pancreatic cancer
Glicosilació alterada
Glicosilación alterada
Altered glycosylation
Marcadors tumorals
Marcadores tumorales
Tumour markers
Glicoproteòmica
Glicoproteómica
Glycoproteomics
Mesotelina (MSLN)
Mesothelin (MSLN)
REG1
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616
616.3
Descripción
Sumario:Pancreatic cancer (PaC) is the deadliest of all tumours, with a 5-year survival below 12% and a mortality/incidence ratio of 94.5%. One of the main reasons behind this dismal prognosis is the diagnosis of the disease at late stages, usually when metastasis have already occurred and no effective therapies are available. Nowadays, there is no accurate tumour marker for the detection of PaC. Only the use of the carbohydrate antigen 19-9 (CA19-9) is clinically validated for the management and recurrence evaluation of the disease, but lacks specificity to be used as a diagnostic test. For this reason, the discovery of novel biomarkers able to detect PaC in early stages, when current therapies are still effective, is of utmost significance for the research and medical communities. Altered glycosylation, a common feature of cancer, stands as a potential source for developing new tumour markers. However, a specific glycan signature to diagnose PaC has not been described. As glycosylation is one of the main post-translational modification of proteins, we hypothesise that the combinatorial analysis of tumour- associated glycan structures on overexpressed PaC proteins could outperform the sensitivity and specificity of current methodologies. In this regard, we have studied the glycosylation pattern of two neo-/over-expressed proteins in PaC, mesothelin (MSLN) and regenerating islet-derived protein 1 (REG1), and we have assessed the potential of their glycoforms as PaC tumour markers