Abstract 1061: MicroRNA profiling by a next generation sequencing approach in urine and plasma samples: from genomics to diagnostics and prognostics of bladder cancer
Authors: Pardini Barbara , Cordero Francesca , Allione Alessandra , Viberti Clara , Naccarati Alessio , Oderda Marco , Preto Mirko , Allasia Marco , Arigoni Maddalena , Riccardo Federica , Calogero Raffaele , Sacerdote Carlotta , Matullo Giuseppe 
Published: July 2016

Abstract
Bladder cancer (BC) is one of the leading causes of cancer-related death worldwide.
Most BCs are non-muscle invasive (NMIBC), which generally have a good prognosis but frequently recur or progress to muscle invasion (MIBC) within 5 years. By contrast, MIBC has a poor prognosis and treatment requires a multidisciplinary approach with radical surgery, radiotherapy, and chemotherapy. BC is among the most expensive cancer per patient because it requires frequent surveillance and repeated treatments over many years.
Reliable predictors of disease and progression for BC are lacking so developing novel noninvasive diagnostics is imperative to both improve patient outcomes and decrease health costs.
MicroRNAs (miRNAs) are aberrantly expressed in many cancers, including BC, and may be isolated from various biological specimens, including plasma and urine.
Next generation sequencing (NGS) technology provides novel information about miRNA expression and is likely to become the gold standard method for comprehensive miRNA analysis in cancer genomics. So far, only few studies investigated miRNA signatures in BC by NGS and only on tissues. To investigate miRNA signatures in surrogate tissues may be a useful alternative to reduce invasiveness of biopsies, allowing repetitive samplings during follow-up and reducing health care costs for detection, monitoring of progression and treatment.
We aim to identify specific miRNA signatures in urine and plasma samples from 20 NMIBC, 20 MIBC patients and 40 healthy controls using a NGS approach able to accurately distinguish BC patients and predict disease outcome. The measurement of miRNA levels in both urine and plasma samples from the same patients will allow us to compare the levels of promising biomarkers in two surrogate tissues. Urine is the best and closest surrogate tissue for BC, since it is in direct contact with the tissue of tumor origin; while plasma is one of the best surrogate tissue for distant metastasis and advanced cancer detection.
In plasma samples, 5 miRNAs were differentially expressed among cases and controls (miR-222, miR-146b, miR-126, miR221 upregulated and miR-5096 downregulated). However, after repetition of the analyses stratifying cases for NMIBC (the most represented group in BC cases), only 2 of the previously described miRNAs (miR-222 and miR-126) resulted dysregulated among NMIBC and controls.
In urine, 31 miRNAs were differentially expressed among BC cases and controls (adjusted p-value ranging from 0.0007 to 0.05). On the other hand, 26 and 31 miRNAs resulted differentially expressed among NMIBC and controls and MIBC and controls, respectively (for NMIBC: adjusted p-value from 0.0009 to 0.04; for MIBC adjusted p-value from 7.2×10-9 to 0.04).
Interestingly, miRNAs differentially expressed among cases and controls were able to discriminate not only BC cases from controls, but also NMIBC and MIBC.
Citation Format: Barbara Pardini, Francesca Cordero, Alessandra Allione, Clara Viberti, Alessio Naccarati, Marco Oderda, Mirko Preto, Marco Allasia, Maddalena Arigoni, Federica Riccardo, Raffaele Calogero, Carlotta Sacerdote, Giuseppe Matullo. MicroRNA profiling by a next generation sequencing approach in urine and plasma samples: from genomics to diagnostics and prognostics of bladder cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1061.