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

Abstract

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.