Abstract

Prostate cancer (PC) is a highly heterogenous disease and one of the leading causes of mortality in developed countries. Recently, studies have shown that expression of immune checkpoint proteins are directly or indirectly repressed by microRNAs (miRs) in many types of cancers. The great advantages of using miRs based therapy is the capacity of these short transcripts to target multiple molecules for the same- or different pathways with synergistic immune inhibition effects. miR-424 has previously been described as a biomarker of poor prognosis in different types of cancers. miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis. In the present study, the clinical significance of miR-424-3p expression in PC tissue was evaluated. Naïve radical prostatectomy specimens from 535 patients was used for tissue microarray construction. In situ hybridization was used to evaluate the expression of miR-424-3p and immunohistochemistry was used for CTLA-4 protein detection. In univariate- and multivariate analyses, low expression of miR-424-3p was significant associated with clinical failure-free survival, (p = 0.004) and p = 0.018 (HR:0.44, CI95% 0.22–0.87). Low expression of miR-424-3p also associated strongly with aggressive phenotype of PC. This highlight the importance of miR-424-3p as potential target for therapeutic treatment in prostate cancer.

Details

Title
Low Expression of miR-424-3p is Highly Correlated with Clinical Failure in Prostate Cancer
Author
Richardsen, E 1 ; Andersen, S 2 ; Al-Saad, S 1 ; Rakaee, M 3   VIAFID ORCID Logo  ; Nordby, Y 4 ; Pedersen, M I 3 ; Ness, N 3 ; Ingebriktsen, L M 3 ; Fassina, A 5 ; Taskén, K A 6 ; Mills, I G 7 ; Donnem, T 2 ; Bremnes, R M 2 ; Busund, L T 1 

1  Translational Cancer Research Group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway 
2  Translational Cancer Research Group, Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway; Department of Oncology, University Hospital of North Norway, Tromso, Norway 
3  Translational Cancer Research Group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway 
4  Translational Cancer Research Group, Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway; Department of Urology, University Hospital of North Norway, Tromso, Norway 
5  Department of Medicine, University of Padua, Padova, Italy 
6  Institute of Cancer Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway 
7  Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK 
Pages
1-10
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-47234-0
ProQuest document ID
2297179277
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.