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

Document Type: Research Articles

Authors

1 Department of Clinical and Chemical Pathology, Kasr Al Ainy Centre of Clinical Oncology and Nuclear Medicine, School of Medicine, Cairo University, Cairo, Egypt.

2 Department of Clinical Oncology, Kasr Al Ainy Centre of Clinical Oncology and Nuclear Medicine, School of Medicine, Cairo University, Cairo, Egypt.

3 Molecular oncology unit, Kasr Al-Ainy Centre of Clinical Oncology and Nuclear Medicine, School of Medicine, Cairo University, Cairo, Egypt.

4 Faculaty of Science, Cairo University, Cairo, Egypt.

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.

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