Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study.

Area of Science:

• Oncology
• Molecular Biology
• Medical Imaging

Background:

• Circulating microRNAs (miRNAs) are emerging biomarkers for various cancers.
• Breast cancer (BC) diagnosis and prognosis can be improved by identifying novel circulating biomarkers.
• Integrating molecular biomarkers with in vivo imaging could enhance understanding of tumor biology.

Purpose of the Study:

• To identify novel circulating miRNAs for accurate breast cancer (BC) diagnosis.
• To correlate miRNA expression with in vivo tumor characteristics assessed by PET/MR imaging.
• To evaluate the diagnostic and prognostic potential of identified miRNAs, individually and in combination with CA15-3.

Main Methods:

• Screening of 84 human miRNAs in plasma from 77 BC patients and 78 healthy controls using miRNA PCR arrays and real-time PCR.
• Correlation analysis of validated miRNA expression with quantitative PET/MR imaging parameters (e.g., SUVmax, ADCmean, Ktrans).
• Assessment of diagnostic accuracy using Receiver Operating Characteristic (ROC) curves and combination analysis with the tumor marker CA15-3.

Main Results:

• Circulating miR-125b-5p (AUC=0.85) and miR-143-3p (AUC=0.80) were upregulated in BC patients and discriminated them from healthy subjects.
• Combining miR-125b-5p with CA15-3 improved diagnostic accuracy from 70% to 89%.
• miR-143-3p correlated with tumor aggressiveness markers, while miR-125b-5p indicated a potentially more favorable prognosis.

Conclusions:

• miR-125b-5p and miR-143-3p are potential biomarkers for breast cancer risk stratification.
• The combination of miR-125b-5p and CA15-3 enhances diagnostic sensitivity for BC detection.
• This study pioneers the correlation of circulating miRNAs with in vivo quantified tumor biology via PET/MR, offering insights into BC pathogenesis.