Publicação
Unraveling Proteomic Disorder and Biomarker Discovery for Bladder Cancer Diagnosis and Treatment
| Resumo: | Bladder cancer is one of the most commonly diagnosed malignancies, generally classi- fied into two major types: Non-Muscle Invasive Bladder Cancer (NMIBC) and Muscle-Inva- sive Bladder Cancer (MIBC). While cystoscopy remains the gold standard for diagnosis, it is an invasive and costly procedure that must be frequently repeated due to the high recurrence rate and the nonspecific nature of bladder cancer symptoms. Therefore, there is a critical need to develop non-invasive diagnostic methods for early detection and monitoring. This study employs a label-free quantitative proteomics approach (quantification with- out the use of isotopes) to identify differentially expressed proteins in 35 patients, including 12 with NMIBC, 12 with MIBC, and 11 with cystitis as a non-cancerous control group. 923 proteins were quantified across these groups (False Discovery rate of 1%). Comparative pro- teomic profiling (two-tailed Student’s t-test between the two groups with permutation-based FDR 0.05 and S0 of 0.1) revealed 25 proteins significantly dysregulated in NMIBC compared to cystitis, suggesting potential biomarkers for distinguishing between malignant and non- malignant inflammatory conditions. In MIBC comparative proteomic profiling with cystitis (two-tailed Student’s t-test between the two groups with permutation-based FDR 0.05 and S0 of 0.1), 564 proteins were differentially expressed, with 177 upregulated and 387 downregu- lated, indicating extensive molecular changes associated with the disease's aggressive nature. Entropy analysis demonstrated increased proteomic disorder in MIBC, reflecting its bi- ological heterogeneity and possibly contributing to variability in therapeutic responses. Fur- ther analysis identified 50 proteins associated with clinical outcomes in bladder cancer, includ- ing COL15A1, HSPG2, and CTSB, which were significantly downregulated in MIBC. These proteins are implicated in tumor progression, loss of protective mechanisms, and cytoskeletal remodeling. The study also discusses potential therapeutic strategies targeting proteins implicated in MIBC, including tyrosine kinase inhibitors, protease inhibitors, and immune-based therapies. However, further validation in independent patient cohorts and functional assays is necessary to confirm the clinical utility of these biomarkers and therapeutic targets. This study provides a comprehensive proteomic landscape of bladder cancer, offering insights into emerging bi- omarkers and therapeutic strategies that may improve bladder cancer diagnosis, prognosis, and treatment outcomes. |
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| Autores principais: | Montes, João de Matos Reis Aleixo |
| Assunto: | Bladder Cancer NMIBC MIBC Drug Targets Non-invasive |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Bladder cancer is one of the most commonly diagnosed malignancies, generally classi- fied into two major types: Non-Muscle Invasive Bladder Cancer (NMIBC) and Muscle-Inva- sive Bladder Cancer (MIBC). While cystoscopy remains the gold standard for diagnosis, it is an invasive and costly procedure that must be frequently repeated due to the high recurrence rate and the nonspecific nature of bladder cancer symptoms. Therefore, there is a critical need to develop non-invasive diagnostic methods for early detection and monitoring. This study employs a label-free quantitative proteomics approach (quantification with- out the use of isotopes) to identify differentially expressed proteins in 35 patients, including 12 with NMIBC, 12 with MIBC, and 11 with cystitis as a non-cancerous control group. 923 proteins were quantified across these groups (False Discovery rate of 1%). Comparative pro- teomic profiling (two-tailed Student’s t-test between the two groups with permutation-based FDR 0.05 and S0 of 0.1) revealed 25 proteins significantly dysregulated in NMIBC compared to cystitis, suggesting potential biomarkers for distinguishing between malignant and non- malignant inflammatory conditions. In MIBC comparative proteomic profiling with cystitis (two-tailed Student’s t-test between the two groups with permutation-based FDR 0.05 and S0 of 0.1), 564 proteins were differentially expressed, with 177 upregulated and 387 downregu- lated, indicating extensive molecular changes associated with the disease's aggressive nature. Entropy analysis demonstrated increased proteomic disorder in MIBC, reflecting its bi- ological heterogeneity and possibly contributing to variability in therapeutic responses. Fur- ther analysis identified 50 proteins associated with clinical outcomes in bladder cancer, includ- ing COL15A1, HSPG2, and CTSB, which were significantly downregulated in MIBC. These proteins are implicated in tumor progression, loss of protective mechanisms, and cytoskeletal remodeling. The study also discusses potential therapeutic strategies targeting proteins implicated in MIBC, including tyrosine kinase inhibitors, protease inhibitors, and immune-based therapies. However, further validation in independent patient cohorts and functional assays is necessary to confirm the clinical utility of these biomarkers and therapeutic targets. This study provides a comprehensive proteomic landscape of bladder cancer, offering insights into emerging bi- omarkers and therapeutic strategies that may improve bladder cancer diagnosis, prognosis, and treatment outcomes. |
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