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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.

Author information

1
Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
2
Departement of Medical Oncology, Brigham and Women's Cancer Center, Brigham and Women's Cancer Center, Boston, MA 02115, USA.
3
Departement of Medical Oncology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
4
The Eli and Edythe L. Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
5
Departement of Medical Oncology, University of Alabama at Birmingham (UAB), 1720 2nd Avenue S, Birmingham, AL 35233, USA.

Abstract

BACKGROUND:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
27351382
PMCID:
PMC4931368
DOI:
10.1038/bjc.2016.146
[Indexed for MEDLINE]
Free PMC Article

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