| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Oto, Julia Herranz, Raquel Plana, Emma Pérez-Ardavín, Javier Hervás, David Cana, Fernando Verger, Patricia Ramos-Soler, David Martínez-Sarmiento, Manuel Vera-Donoso, César D. Medina, Pilar |
| Abstract | We aimed to identify a profile of urine microRNAs (miRNAs) with diagnostic and stratification potential in the whole range of bladder cancer (BC) categories, to avoid current invasive, harmful and expensive procedures. We collected a first morning urine sample from the screening (35 BC patients and 15 age- and gender-matched controls) and validation cohorts (172 BC and 94 controls). In the screening stage we analyzed the expression level of 179 miRNAs by real-time reverse transcription quantitative PCR in urine supernatants. miRNA levels in each sample were normalized by the levels of the previously identified and stably expressed miR-29c-3p. We performed an ordinal regression for each miRNA with False Discovery Rate (FDR) adjustment to identify dysregulated miRNAs, and an ordinal elastic net logistic regression model to identify a miRNA profile for BC diagnosis and stratification with the software R (v3.5.1). Next, we validated the most dysregulated miRNAs, and empirically identified the real miRNA targets in BC cells by miR-eCLIP immunoprecipitation and sequencing. We identified 70 dysregulated miRNAs in BC patients (p < 0.05 FDR-adjusted). With the expression level of 7 miRNAs in urine (miR-221-3p, miR-93-5p, miR-362-3p, miR-191-5p, miR-200c-3p, miR-192-5p, miR-21-5p) we could stratify BC patients and control subjects. To enable the global use of our model, we developed the free BladdermiRaCan online tool. Furthermore, we identified miR-21-5p, miR-425-5p and miR-99a-5p as follow-up markers for BC relapse, and miR-21-5p and miR-221-3p as markers for metastasis. These miRNAs were also dysregulated in BC tissue sections from a subgroup of patients from which urine samples were studied. In conclusion, we have validated and patented a 7-miRNAs urine profile able to diagnose and stratify BC patients; BladdermiRaCan will enable the global use of our model. The experimentally verified target proteins identified for these miRNAs may unravel novel therapeutic targets. |
| Related Links | https://ehoonline.biomedcentral.com/counter/pdf/10.1186/s40164-025-00649-0.pdf |
| Ending Page | 6 |
| Page Count | 6 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 21623619 |
| DOI | 10.1186/s40164-025-00649-0 |
| Journal | Experimental Hematology & Oncology |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-04-11 |
| Access Restriction | Open |
| Subject Keyword | Hematology Oncology Cancer Research Biomarker BladdermiRaCan Bladder cancer Diagnosis miR-eCLIP Immunoprecipitation Liquid biopsy microRNA Prognosis Stratification Urine |
| Content Type | Text |
| Resource Type | Correspondence |
| Subject | Hematology Oncology Cancer Research |
| Journal Impact Factor | 9.4/2023 |
| 5-Year Journal Impact Factor | 8.3/2023 |
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