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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10990/804

Autori: Pin, Elisa
Supervisore afferente all'Università: CURCIO, FRANCESCO
Titolo: Identification of new candidate biomarkers for prostate cancer by affinity proteomics
Abstract (in inglese): Prostate cancer (PCA) is a complex malignancy that needs to be more thoroughly studied and understood at a molecular level to fill the current knowledge gap, and optimize diagnosis and to treatment. Prostate specific antigen (PSA) showed to be not specific for PCA, therefore a demand for novel specific biomarkers exists. The aim of our work was to identify new specific candidate biomarkers for PCA in tissue and plasma samples by means of affinity proteomics approaches such as reverse phase protein array and antigen arrays. Tissue samples are an invaluable source of biomarkers for cancer, but very limited in amount and requiring invasive procedures for collection. Still, they allow to directly profiling the molecular status of tumor itself. Beside tissue, a screening procedure on biological fluid such as plasma would be highly desirable, thanks to the less invasiveness and low-costs of samples collection. Among the biomarkers detectable in plasma are the autoantibodies. The first part of this thesis summarizes the current status of PCA epidemiology, treatment, and biomarkers research. Beside this, an overview of the affinity proteomics platforms available for biomarkers research, and the critical variables to consider in the biomarkers validation process are presented. The second part of the thesis reports the main results of two original studies where the author of the thesis is the main contributor. Paper I is based on the profiling of PCA tissue samples using RPPA. Our results indicate the feasibility of combining laser capture microdissection (LCM) and RPPA for evaluating the molecular architecture and cross-talking of epithelial and stromal compartments. Paper II is based on profiling the autoimmune response to PCA patients, comparing early and late stage of the disease. The authors identified and characterized the IgG reactivity toward a novel epitope for the candidate biomarker prostein. The data presented in this thesis provide two robust frameworks based on affinity proteomics platforms applied for protein profiling in tissue, and autoantibodies profiling in plasma in the context of PCA biomarkers discovery.
Parole chiave: Biomarkers; Proteomics; Prostate cancer; Affinity proteomics; Arrays; Autoimmunity; Phosphoproteomics
MIUR : Settore MED/05 - Patologia Clinica
Lingua: eng
Data: 29-mar-2017
Corso di dottorato: Dottorato di ricerca in Medicina cellulare e molecolare
Ciclo di dottorato: 29
Università di conseguimento titolo: Università degli Studi di Udine
Luogo di discussione: Udine
Altre informazioni: Co-supervisors: Peter Nilsson (Biotechnology Department, KTH-Royal Institute of Technology, Stockholm, Sweden), Mariaelena Pierobon (Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA)
Citazione: Pin, E. Identification of new candidate biomarkers for prostate cancer by affinity proteomics. (Doctoral Thesis, Università degli Studi di Udine, 2017).
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