title: Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression.
abstract: Bladder cancer is the second most frequent malignancy of the urinary tract after prostate cancer. Current diagnostic techniques, such as cystoscopy and biopsies are highly invasive and accompanied of undesirable side effects. Moreover, there are no suitable biomarkers for relapse or progression prognosis. We analysed whether the specific composition of microRNAs (miRNAs) and proteins of extracellular vesicles (EVs) that urothelial tumour cells of bladder mucosa release into the urine, could reflect their pathologic condition. For this purpose, urinary EVs were isolated and their protein and miRNA composition evaluated in healthy donors and low or high-grade bladder cancer patients. Using a microarray platform containing probes for 851 human miRNAs we found 26 deregulated miRNAs in high-grade bladder cancer urine EVs, from which 23 were downregulated and 3 upregulated. Real-time PCR analysis pointed to miR-375 as a biomarker for high-grade bladder cancer while miR-146a could identify low-grade patients. Finally, several protein markers were also deregulated in EVs from tumour patients. Our data suggest that the presence of ApoB in the 100,000 pellet is a clear marker for malignancy.
authors.affiliation: Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Andreu
authors.affiliation: Servicio de Urología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Spain.
authors.forename: Renan
authors.initials: R
authors.lastname: Otta Oshiro
authors.affiliation: Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Redruello
authors.affiliation: Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
authors.forename: Soraya
authors.initials: S
authors.lastname: López-Martín
authors.affiliation: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP); Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Unidad de Proteómica, CBM-SO, Madrid, Spain; Departamento de Biología Molecular, UAM/CBM-SO, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez-Vázquez
authors.affiliation: Unidad de Proteómica, CBM-SO, Madrid, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Morato
authors.affiliation: Unidad de Proteómica, CBM-SO, Madrid, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Marina
authors.affiliation: Servicio de Urología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Olivier Gómez
authors.affiliation: Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain; Departamento de Biología Molecular, UAM/CBM-SO, Madrid, Spain. Electronic address: maria.yanez@salud.madrid.org.
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053299:Apolipoprotein B-100 / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D045744:Cell Line, Tumor; D018450:Disease Progression; D000067128:Extracellular Vesicles / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000652:urine*
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Apo B; Bladder cancer; Extracellular vesicles; MicroRNAs; Proteomics; Urine