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Br J Cancer. 2016 Jun 28;115(1):12-9. doi: 10.1038/bjc.2016.146. Epub 2016 Jun 23.

Association of tumour microRNA profiling with outcomes in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy.

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Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Departement of Medical Oncology, Brigham and Women's Cancer Center, Brigham and Women's Cancer Center, Boston, MA 02115, USA.
Departement of Medical Oncology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
The Eli and Edythe L. Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Departement of Medical Oncology, University of Alabama at Birmingham (UAB), 1720 2nd Avenue S, Birmingham, AL 35233, USA.



Tumour expression of selected microRNAs (miRs) correlates with cisplatin efficacy in multiple cancers. We investigated the role of selected miRs in patients receiving cisplatin-based therapy for advanced urothelial carcinoma (UC).


RNA was extracted from formalin-fixed paraffin-embedded tumour from 83 advanced UC patients who received cisplatin. A miR panel based on relevance for platinum sensitivity and UC was studied by quantitative reverse transcription quantitative PCR (RT-qPCR). Association of progression-free survival (PFS) with miR expression was analysed using cox regression. Selected TFs were chosen by association with the panel of miRs using the Transcription Regulation algorithm (GeneGo MetaCore+MetaDrug version 6.23 build 67496). Bladder cancer (BC) cell lines were used to investigate the previously described role of miR-21 mediating cisplatin sensitivity.


The 83 patients had a median PFS of 8 months. In multivariate analysis, higher levels of E2F1 (P=0.01, HR: 1.95 (1.14, 3.33)), miR-21 (P=0.01, HR: 2.01 (1.17, 3.45)) and miR-372 (P=0.05, HR: 1.70 (1.00, 2.89)) were associated with a shorter PFS. In the 8 BC cell lines, miR-21 was not shown to be necessary nor sufficient for modulating cisplatin sensitivity.


In metastatic UC patients treated with cisplatin-based therapy, high primary tumour levels of E2F1, miR-21 and miR-372 are associated with poor PFS independent of clinical prognostic factors. The in vitro study could not confirm miR-21 levels role in modulating platinum sensitivity.

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