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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| 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 577 616 616.3 |
| 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 |
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