Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status
| Autor: | Carla Oliveira, Jesús M. Paramio, Mónica Martínez-Fernández, Patrícia Oliveira, Cristian Suárez-Cabrera, Felipe Villacampa, Abel Sousa, Andrés Pérez-Figueroa, Marta Dueñas |
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| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genes myc lcsh:Medicine Tumor initiation Kaplan-Meier Estimate medicine.disease_cause Whole Exome Sequencing Exon 0302 clinical medicine Neoplasm Proteins / genetics Recurrence Papilloma / pathology Gene expression Carcinoma Transitional Cell / genetics lcsh:Science Exons / genetics Regulation of gene expression Mutation Multidisciplinary biology Bladder cancer Ciencias de la Salud::Urología y nefrología [Materias Investigacion] Proto-Oncogene Proteins c-mdm2 / genetics Proto-Oncogene Proteins c-mdm2 Exons Prognosis Neoplasm Proteins Gene Expression Regulation Neoplastic Mdm2 Papilloma / genetics Urinary Bladder Neoplasms / pathology Bladder Mutation Missense Article Disease-Free Survival Proto-Oncogene Proteins c-myc 03 medical and health sciences Carcinoma Transitional Cell / pathology Exome Sequencing medicine Humans Neoplasm Invasiveness Carcinoma Transitional Cell Proto-Oncogene Proteins c-myc / genetics Papilloma business.industry E2F Transcription Factors / genetics Alternative splicing lcsh:R medicine.disease Genes p53 E2F Transcription Factors Alternative Splicing 030104 developmental biology Gene Ontology Urinary Bladder Neoplasms Tissue Array Analysis Cancer research biology.protein Neoplasm Proteins / biosynthesis lcsh:Q business 030217 neurology & neurosurgery Urinary Bladder Neoplasms / genetics |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Dadun. Depósito Académico Digital de la Universidad de Navarra instname Scientific Reports |
| Popis: | Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis. We express our deepest acknowledgement to patients and their families. The authors also acknowledge the computing resources and technical support provided by Abel Paz-Gallardo and Alfonso Pardo from Extremadura Research Centre for Advanced Technologies (CETA−CIEMAT). This work was supported FEDER cofounded MINECO grant SAF2015-66015-R, ISCIII-RETIC RD12/0036/0009, and PIE15/00076 and CB/16/00228 (to J.M. Paramio); MMF was supported by a Jose Castillejo Fellowship (CAS16/00115). |
| Databáze: | OpenAIRE |
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