Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer-A Multi-Institutional Study

Maria J Stoen; Sigve Andersen; Mehrdad Rakaee; Mona I Pedersen; Lise M Ingebriktsen; Tom Donnem; Ana P G Lombardi; Thomas K Kilvaer; Lill-Tove R Busund; Elin Richardsen

doi:10.3390/cancers13164096

Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer-A Multi-Institutional Study

Cancers (Basel). 2021 Aug 14;13(16):4096. doi: 10.3390/cancers13164096.

Authors

Maria J Stoen¹, Sigve Andersen^{2

3}, Mehrdad Rakaee^{2

4}, Mona I Pedersen², Lise M Ingebriktsen^{1

5}, Tom Donnem^{2

3}, Ana P G Lombardi¹, Thomas K Kilvaer^{1

3}, Lill-Tove R Busund^{1

6}, Elin Richardsen^{1

6}

Affiliations

¹ Translational Cancer Research Group, Institute of Medical Biology, UiT The Arctic University of Norway, N-9037 Tromso, Norway.
² Translational Cancer Research Group, Institute of Clinical Medicine, UiT The Arctic University of Norway, N-9037 Tromso, Norway.
³ Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway.
⁴ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁵ Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, N-5021 Bergen, Norway.
⁶ Department of Clinical Pathology, University Hospital of North Norway, N-9038 Tromso, Norway.

Abstract

Objective: assessing the prognostic role of miR-20a-5p, in terms of clinical outcome, in a large multi-institutional cohort study.

Methods: Tissue microarrays from 535 patients' prostatectomy specimens were constructed. In situ hybridization was performed to assess the expression level of miR-20a-5p in different tissue subregions: tumor stroma (TS) and tumor epithelium (TE). In vitro analysis was performed on prostate cancer cell lines.

Results: A high miR-20a-5p expression was found negatively in association with biochemical failure in TE, TS and TE + TS (p = 0.001, p = 0.003 and p = 0.001, respectively). Multivariable analysis confirmed that high miR-20a-5p expression in TE independently predicts dismal prognosis for biochemical failure (HR = 1.56, 95% CI: 1.10-2.21, p = 0.014). Both DU145 and PC3 cells exhibited increased migration ability after transient overexpression of miR-20a-5p, as well as significant elevation of invasion in DU145 cells.

Conclusion: A high miR-20a-5p expression in tumor epithelium is an independent negative predictor for biochemical prostate cancer recurrence.

Keywords: biomarker; miR-20a-5p; microRNA; prognostication; prostate cancer; radical prostatectomy.

Grants and funding

16-2551/Kreftforeningen