Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Joaquim Bellmunt  1   2   3 , Chensheng Willa Zhou  1 , Stephanie A Mullane  1 , Lillian Werner  1 , Mary-Ellen Taplin  1   3 , André P Fay  1 , Toni K Choueiri  1   2   3 , Anna Orsola  1 , David Y Takeda  1   2   3 , William C Hahn  1   2   3   4 , Jaegil Kim  4 , Guru Sonpavde  5 , Michaela Bowden  1
Affiliations

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

Joaquim Bellmunt et al. Br J Cancer. .

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.

PubMed Disclaimer

Conflict of interest statement

JB: consultant for Pierre Fabre, Astellas, Pfizer, Merck and Genentech. Research funding from Takeda and Sanofi. GS: research support from Onyx, Bayer and Boehringer-Ingelheim; advisory board/consultant for Merck, Genentech, Sanofi, Bayer, Pfizer and Novartis. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Progression-free survival (PFS) based on high tumour miRNA levels of miR-21 (A), miR-372 (B), E2F1 (C) and combination of miR-21 and E2F1 (D).
Figure 2
Figure 2
Sensitivity of bladder cancer cell lines to cisplatin in vitro.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Akagi I, Okayama H, Schetter AJ, Robles AI, Kohno T, Bowman ED, Kazandjian D, Welsh JA, Oue N, Saito M, Miyashita M, Uchida E, Takizawa T, Takenoshita S, Skaug V, Mollerup S, Haugen A, Yokota J, Harris CC (2013) Combination of protein coding and noncoding gene expression as a robust prognostic classifier in stage I lung adenocarcinoma. Cancer Res 73(13): 3821–3832. - PMC - PubMed
    1. Alla V, Engelmann D, Niemetz A, Pahnke J, Schmidt A, Kunz M, Emmrich S, Steder M, Koczan D, Putzer BM (2010) E2F1 in melanoma progression and metastasis. J Natl Cancer Inst 102(2): 127–133. - PubMed
    1. Apolo AB, Ostrovnaya I, Halabi S, Iasonos A, Philips GK, Rosenberg JE, Riches J, Small EJ, Milowsky MI, Bajorin DF (2013) Prognostic model for predicting survival of patients with metastatic urothelial cancer treated with cisplatin-based chemotherapy. J Natl Cancer Inst 105(7): 499–503. - PMC - PubMed
    1. Bajorin DF, Dodd PM, Mazumdar M, Fazzari M, McCaffrey JA, Scher HI, Herr H, Higgins G, Boyle MG (1999) Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol 17(10): 3173–3181. - PubMed
    1. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2): 281–297. - PubMed

Publication types

LinkOut - more resources