Evaluation of secretome-associated proteins as potential biomarkers in glioblastoma

• Autor(a) principal: Alves, Bárbara Couto Viana
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.22/21540
• topic: Glioblastoma; Secretome; Biomarkers; Immunohistochemistry; Plasma

Glioblastoma (GB) is the most agressive central nervous system tumor and the one of the deadliest human cancers. It remains diagnosed at late stages when cure is, most often, not possible, highlighting the need for effective biomarkers for clinical management. GB secretome holds tremendous potential as a source of biomarkers, strengthened by the possibility for their detection in patient body fluids (e.g., blood/plasma). Among the most frequently described proteins found differentially expressed in GB patients’ plsma are MMP-2, MMP-9, YKL40, VEGFA, and osteopontin. Still, to date, none of them have shown to fulfil a relevant clinical role as a biomarker. This project aims to evaluate the expression of these proteins in GB tumor tissue and plasma samples, using immunohistochemistry and proteomic analysis, respectively, and to associate their expression with patients’ clinicopathological data and survival. In the series of B tissues evaluated, while VEGFA expression was heterogeneous. Importantly, VEGFA and YKL40 expression signifiantly impacted patients’ progression-free survival (after temozolomide/bevacizumab treatment). Moreover, proteomic analysis of a restricted number of GB plasma samples showed increased MMP-9 levels compared to controls. This study supports the relevance of studying secretome-associated proteins as GB biomarkers. In particular, it unveiled VEGFA and YKL40 as promising biomarkers to predict response to therapy.