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

被引：13

作者：

Stoen, Maria J. ^{[1
]}

Andersen, Sigve ^{[2
,3
]}

Rakaee, Mehrdad ^{[2
,4
]}

Pedersen, Mona, I ^{[2
]}

Ingebriktsen, Lise M. ^{[1
,5
]}

Donnem, Tom ^{[2
,3
]}

Lombardi, Ana P. G. ^{[1
]}

Kilvaer, Thomas K. ^{[1
,3
]}

Busund, Lill-Tove R. ^{[1
,6
]}

Richardsen, Elin ^{[1
,6
]}

机构：

[1] UiT Arctic Univ Norway, Inst Med Biol, Translat Canc Res Grp, N-9037 Tromso, Norway

[2] UiT Arctic Univ Norway, Inst Clin Med, Translat Canc Res Grp, N-9037 Tromso, Norway

[3] Univ Hosp North Norway, Dept Oncol, N-9038 Tromso, Norway

[4] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[5] Univ Bergen, Ctr Canc Biomarkers CCBIO, Dept Clin Med, Sect Pathol, N-5021 Bergen, Norway

[6] Univ Hosp North Norway, Dept Clin Pathol, N-9038 Tromso, Norway

来源：

CANCERS | 2021年 / 13卷 / 16期

关键词：

prostate cancer; microRNA; miR-20a-5p; radical prostatectomy; biomarker; prognostication; CIRCULATING MICRORNAS; EXPRESSION; CLUSTER; PROGRESSION; PREDICTION; BIOMARKERS; DIAGNOSIS; MIR-17-92; GENOMICS; PROPOSAL;

D O I：

10.3390/cancers13164096

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary MicroRNAs (miRs) have critical regulatory roles in cell functions, and are involved in prostate cancer tumorigenesis. miR-20a-5p is a member of the oncogenic miR-17-92 cluster. Overexpressed miR-20a-5p has been shown to increase both cell proliferation and cell migration in cancers. The aim of our cohort study was to evaluate the prognostic role of miR-20a-5p in prostate cancer. We found miR-20a-5p associated with biochemical failure in tumor epithelium and tumor stroma. In the multivariable analysis miR-20a-5p in tumor epithelium was found to be an independent prognostic predictor for biochemical failure. In the functional studies, migration and invasion were significantly increased in miR-20a-5p transfected prostate cancer cell lines. In conclusion, high miR-20a-5p expression in tumor epithelium is a negative independent prognostic factor for biochemical failure in prostate cancer. 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.

引用

页数：15