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.
Scientific reports. 2019 Jul 17*** epublish ***
Marta Dueñas, Andrés Pérez-Figueroa, Carla Oliveira, Cristian Suárez-Cabrera, Abel Sousa, Patricia Oliveira, Felipe Villacampa, Jesús M Paramio, Mónica Martínez-Fernández
Molecular Oncology Unit, CIEMAT, Avda Complutense 40, 28040, Madrid, Spain., Phylogenomics Lab. Department of Biochemistry, Genetics an Immunology & Biomedical Research Center (CINBIO), University of Vigo, 36310, Vigo, Spain., Expression Regulation in Cancer Lab, Universidade do Porto, i3s & IPATIMUP. Rua Alfredo Allen, 208, 4200-135, Porto, Portugal., Biomedical Research Institute, Hospital Universitario 12 de Octubre, Avda Córdoba s/n, 28041, Madrid, Spain., Molecular Oncology Unit, CIEMAT, Avda Complutense 40, 28040, Madrid, Spain. ., Molecular Oncology Unit, CIEMAT, Avda Complutense 40, 28040, Madrid, Spain. .