Circulating miR-34a and miR-125b as Promising non Invasive Biomarkers in Egyptian Locally Advanced Breast Cancer Patients

Asian Pac J Cancer Prev. 2019 Sep 1;20(9):2749-2755. doi: 10.31557/APJCP.2019.20.9.2749.

Abstract

Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group of non-coding, single stranded RNAs of ~ 22 nucleotides, which regulate gene expression at the post-transcriptional level. Circulating miRNAs have been found as potential blood based predictive biomarkers. Purpose: we aim to evaluate miR-34a and miR-125b to predict outcome from neoadjuvant chemotherapy in Egyptian BC patients. Methodology: Quantitative assessment of plasma miR-34a and miR-125b expression was performed by qRT-PCR. Thirty nine newly diagnosed locally advanced BC female patients with 10 age and sex matched healthy volunteers were included in the study. Results: We performed ROC curve analysis to evaluate the diagnostic value for the miR-34a with AUCs = 0.995, cutoff point of 2.57 sensitivity 97.4%, specificity 100%, PPV 100%, NPV 83.3% and accuracy 97.7%. miR-125b had AUC = 0.68 and a cutoff point of 8.69 with sensitivity 66.7%, specificity 70.0%, PPV 90.6%, NPV 41.2% and accuracy 73.5%. miR-34a expression were significantly higher in BC patients compared to controls with p value <0.001*. Also, miR-34a expression level was significantly higher in patients with progressive disease with P value =0.03*. However, miR-125b expression levels were insignificantly higher in responsive patients with p value = 0.2. Conclusion: miRNAs are crucial candidates for novel molecular targeted therapies due to their capability to regulate numerous genes in molecular pathways. Our data suggest that circulating miR-34a and miR-125b expression levels could be promising highly accurate non-invasive biomarkers in diagnosing BCs. miR-34a can predict chemotherapeutic resistance associated with higher expression levels in non-responsive patients.

Keywords: Biomarker; Circulating microRNA; Neoadjuvant chemotherapy; breast cancer.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Lobular / blood
  • Carcinoma, Lobular / drug therapy
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / pathology*
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / genetics*
  • Egypt
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MIRN125 microRNA, human
  • MIRN34 microRNA, human
  • MicroRNAs