Circulating microRNAs and serum proteins in breast cancer patients: Diagnostic relevance and grade-specific expression patterns.

BACKGROUND: Breast cancer is a prominent contributor to female cancer-related mortality. Early detection and accurate diagnosis are essential for effective management. AIM: To evaluate the diagnostic relevance of a panel of circulating microRNAs (miRNAs) independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade. METHODS: In the present study, we analyzed the aberrant expression of miR-21, miR-221, miR-1246, miR-145, and miR-382, in addition to the tumor biomarkers cancer antigen 15-3 (CA15-3) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in breast cancer patients with varying grades. RESULTS: Our results revealed distinct expression patterns of these miRNAs between grade II and III patients. Specifically, miR-21, miR-221, and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG were observed in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacy in differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggesting their interconnected roles in breast cancer progression. Receiver operating characteristic curve analysis demonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing the highest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancer grades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanced diagnostic accuracy and sensitivity. CONCLUSION: These findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patients based on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting the development of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management of breast cancer patients.