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 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.
Translational Cancer Research Group, Dept Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept Oncology, University Hospital of North Norway, 9038 Tromso, Norway.
Sigve
S
Andersen
Translational Cancer Research Group, Dept of Medical Biology, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept Pathology, University Hospital of North Norway, 9038 Tromso, Norway.
Elin
E
Richardsen
Translational Cancer Research Group, Dept of Medical Biology, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept Pathology, University Hospital of North Norway, 9038 Tromso, Norway.
Line
L
Moi
Translational Cancer Research Group, Dept Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept Oncology, University Hospital of North Norway, 9038 Tromso, Norway.
Tom
T
Donnem
Translational Cancer Research Group, Dept Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept of Urology, University Hospital of North Norway, 9038 Tromso, Norway.
Yngve
Y
Nordby
Translational Cancer Research Group, Dept of Medical Biology, UiT, The Arctic University of Norway, 9037 Tromso, Norway.
Nora
N
Ness
Translational Cancer Research Group, Dept Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept Oncology, University Hospital of North Norway, 9038 Tromso, Norway.
Marte Eilertsen
ME
Holman
Translational Cancer Research Group, Dept Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept Oncology, University Hospital of North Norway, 9038 Tromso, Norway.
Roy M
RM
Bremnes
Translational Cancer Research Group, Dept of Medical Biology, UiT, The Arctic University of Norway, 9037 Tromso, Norway.|Dept Pathology, University Hospital of North Norway, 9038 Tromso, Norway.
Lill-Tove
LT
Busund
D000368:Aged; D018572:Disease-Free Survival; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate
C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm