Fibroblast miR-210 overexpression is independently associated with clinical failure in Prostate Cancer – a multicenter (in situ hybridization) study

There is a need for better prognostication in prostate cancer (PC). “The micromanager of hypoxia”, microRNA-210 (miR-210) is directly linked to hypoxia, is overexpressed in PC and has been implied in tumor cell-fibroblast crosstalk. We investigated the prognostic impact of miR-210 in tumor cells and...

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Bibliographic Details
Published in:Scientific reports 2016-11, Vol.6 (1), p.36573-36573, Article 36573
Main Authors: Andersen, Sigve, Richardsen, Elin, Moi, Line, Donnem, Tom, Nordby, Yngve, Ness, Nora, Holman, Marte Eilertsen, Bremnes, Roy M., Busund, Lill-Tove
Format: Article
Language:English
Subjects:
631/67/1857
692/4017
692/4028/67/589/466
692/53/2422
Cancer surgery
Clinical medical disciplines: 750
Fibroblasts
Humanities and Social Sciences
Hybridization
Hypoxia
Klinisk medisinske fag: 750
Medical disciplines: 700
Medisinske Fag: 700
miRNA
multidisciplinary
Oncology: 762
Onkologi: 762
Prostate cancer
Prostatectomy
Science
Studies
Survival
Tumor cells
Tumors
VDP
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Summary:There is a need for better prognostication in prostate cancer (PC). “The micromanager of hypoxia”, microRNA-210 (miR-210) is directly linked to hypoxia, is overexpressed in PC and has been implied in tumor cell-fibroblast crosstalk. We investigated the prognostic impact of miR-210 in tumor cells and fibroblasts in PC. Tumor and stromal samples from a multicenter PC cohort of 535 prostatectomy patients were inserted into tissue microarrays. To investigate the expression of miR-210, we used in situ hybridization and two pathologists semiquantitatively scored its expression. Overexpression of miR-210 in tumor cells was not associated to biochemical failure-free survival (BFFS, p = 0.85) or clinical failure-free survival (CFFS, p = 0.09). However, overexpression of miR-210 in fibroblasts was significantly associated to a poor CFFS (p = 0.001), but not BFFS (p = 0.232). This feature was validated in both cohorts. Overexpression of miR-210 was independently associated with a reduced CFFS (HR = 2.76, CI 95% 1.25–6.09, p = 0.012). Overexpression of miR-210 in fibroblasts is independently associated with a poor CFFS. This highlights the importance of fibroblasts and cellular compartment crosstalk in PC. miR-210 is a candidate prognostic marker and potential therapeutic target in PC.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep36573