MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer

Charis Kalogirou,Maximilian Burger,Evelyne Lerut,Hubertus Riedmiller,Martin Spahn,Burkhard Kneitz,Markus Krebs,Steven Joniau,Susanne Kneitz,Claus-Jürgen Scholz

doi:10.3390/ijms141121414

Abstract

The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.

Highlights

High-risk prostate cancer (HRPCa, defined by Gleason score ≥ 8 and/or Pathological Stage (pT) ≥ 3 and/orPSA ≥ 20 ng/μL) is a PCa subgroup with varying risk of biochemical progression (BCR), clinical failure (CF) and cancer-specific mortality (CSM) following radical prostatectomy [1]
These results demonstrate that miR-205 acts as a tumour suppressor in PCa cells by regulating cell growth and invasiveness
Our present data promote a tumour-suppressive role of miR-205 in high-risk prostate cancer (HRPCa) due to its frequent down-regulation in tumourous tissue

Summary

Introduction

PSA ≥ 20 ng/μL) is a PCa subgroup with varying risk of biochemical progression (BCR), clinical failure (CF) and cancer-specific mortality (CSM) following radical prostatectomy [1]. While the key event of lymph node metastasis, which often remains undiscovered prior to initial treatment, impacts significantly upon management, reliable preoperative detection with current diagnostic imaging remains unsatisfactory [3]. New prognostic markers for HRPCa are necessary, especially if therapeutic targets are to be met. Alterations of miR expression were detected in various cancer entities including PCa [7,8,9,10,11,12,13,14]. MiR expression profiles stratify cancers by clones and level of differentiation suggesting that miRs are involved in cancer progression [9,10]

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