The prognostic role of epigenetic dysregulation in bladder cancer: A systematic review |
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| Institution: | 1. Cancer Research Program, PSMAR-IMIM (Hospital del Mar Medical Research Institute), Carrer Dr. Aiguader 88, 08003 Barcelona, Spain;2. Universitat Pompeu Fabra, Plaça de la Mercè 10, 08002 Barcelona, Spain;3. Dana-Farber Cancer Institute, 450 Brookline Ave, DANA 1230, Boston, MA 02215, USA;1. Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY;2. Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, NY;3. Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY;4. Department of Pathology, Case Western Reserve University, Cleveland, OH;5. Department of Medical Oncology, Indiana University Simon Cancer Center, Indianapolis, IN;6. Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY;7. Department of Medical Oncology, Inova Comprehensive Cancer Research Institute, Falls Church, VA;1. Department of Urologic Sciences, University of British Columbia, Vancouver, Canada;2. Department of Urology, University of Bern, Bern, Switzerland;1. Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands;2. Laboratory and Department of Urology, Hospital Clínic, Institut d''Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain;3. CIBERehd, Plataforma de Bioinformática, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain;4. Pathology Department, Hospital Clínic, Institut d''Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain;1. Department of Urology, Clinical Sciences Malmö, Skåne University Hospital, Lund University, Malmö, Sweden;2. Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden;3. Department of Urology, Helsingborg Hospital, Helsingborg, Sweden;4. Tullgatan 1 B, Lund, Sweden |
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| Abstract: | BackgroundDespite adequate treatment and follow-up, around one fifth of patients with localized bladder cancer will present with disease progression. Adequate prognostic biomarkers are lacking to define patients who are at risk. Mutations in chromatin remodeling genes are more frequently found in bladder cancer than in any other solid tumor. However, the prognostic relevance of epigenetic dysregulation has not been established and may offer an opportunity for biomarker discovery.MethodsLooking for prognostic epigenetic factors, we performed a comprehensive PubMed search using keywords such as “bladder cancer”, “chromatin remodeling”, “gene methylation” and “epigenetics”. We only included studies reporting on the association of epigenetic markers with prognostic outcomes such as recurrence, progression or survival.ResultsOf 1113 results, 87 studies met the inclusion criteria, which represented a total of 85 epigenetic markers with potential prognostic relevance. No prospective studies were identified. Seventy-three percent (64/87) of the studies involved mixed cohorts of muscle invasive and non-muscle invasive bladder cancer. Promoter methylation of genes with putative prognostic value affected cellular processes such as cell cycle, apoptosis, cell-adhesion or migration, as well as critical pathways such as MAP-kinase or Wnt. Alteration of chromatin regulatory elements suggest a prognostic relevance alterations leading to a predominantly silenced chromatin state.ConclusionsThe prognostic impact of epigenetic alterations in bladder cancer is still unclear. Prospective evaluation of methylation marks and chromatin remodeling gene alterations using consistent methods and criteria is warranted. |
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| Keywords: | Urothelial carcinoma Methylation Chromatin remodeling Non-coding RNA Prognosis Recurrence Progression |
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