Comparative analysis of epi-miRNA expression levels in local/locally advanced and metastatic prostate cancer patients

Gene. 2020 Oct 20;758:144963. doi: 10.1016/j.gene.2020.144963. Epub 2020 Jul 17.

Abstract

Abnormal expression of enzymes involved in epigenetic mechanisms, such as DNA methyl transferases, can trigger large chaos in cellular gene expression networks and eventually lead to cancer progression. In our study, which is a pioneer in the literature that clinicopathologically evaluates the expression of 30 epi-miRNAs in prostate cancer (PCa), we investigated which of the new miRNA class epi-miRNAs could be an effective biomarker in the diagnosis and progression of PCa. In this study, the expression levels of 30 epi-miRNAs in whole blood samples from 25 control, 25 PCa and 40 metastatic PCa patients were investigated by the Quantitative Real-Time PCR method. Then, promoter methylation levels of 11 epi-miRNAs, whose expression levels were found to be significantly higher, were examined by methylation-specific qPCR method. The correlations between miRNA expression levels and clinicopathological parameters (Gleason Score (GS), PSA levels, TNM Staging) in different stages of PCa groups as well as disease-specific expression levels were examined. We found a hypomethylation in the promoter regions of miRNAs that showed a direct proportional increase with PSA levels (miR-34b/c, miR-148a, miR-152), GS's (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-148a, miR- 152, miR-185-5p) and T staging (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-140, miR-148a, miR-152, miR-185-5p) (p < 0.05). When miR-200a/b was evaluated according to clinicopathological parameters, it acted as an onco-miR in local/local advanced PCa and as a tumor-suppressor-miR in metastatic stage. This study is novel in the sense that our findings draw attention to the important role of miRNAs as diagnostic and prognostic biomarkers in PCa.

Keywords: Biomarkers; DNA methylation; Epi-microRNAs; Prognosis; Prostate cancer.

MeSH terms

  • Biomarkers, Tumor / genetics
  • DNA Methylation / genetics*
  • Epigenesis, Genetic / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Grading
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Prostate-Specific Antigen