Breast cancer (BC) is the second leading cause of cancer-related death among women worldwide. Within Asia, the incidence of BC is highest among Pakistani women and it is estimated that every ninth women is at risk of BC in her life. Early diagnosis via reliable non-invasive biomarkers is crucial in successful management of BC patients. MicroRNAs (miRNAs) regulate biological processes via post-transcriptional regulation of their target genes. Interestingly, miRNAs are also stably expressed in body fluids and are reflective of disease pathology, thus can act as novel disease biomarkers. In the present study, a combination of five oncogenic/tumor-suppressor miRNAs (miR-21-5p -221-3p, -155-5p, -146a-5p, -99b) was evaluated as potential diagnostic biomarkers for BC.
The present case-control study comprised of 140 age-matched participants (pre-operative/treatment-naive BC (n) = 80; non-cancerous healthy controls (n) = 60). The expression levels of selected miRNAs were then measured via qPCR followed by statistical analysis to compute expression differences and clinical correlations among groups. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic potential of miRNAs.
The miR-21, miR-155 and miR-221 levels were significantly upregulated in BC patients in comparison to controls (P = 6.3 x 10-3, P = 2.68 x 10-2 and P = 9 x 10-4 respectively) whereas, miR-146a and miR-99b were non-significant. miR-221 levels were significantly elevated in ER+ patients in comparison to ER- and correlated with tumor status (P < 0.01). Furthermore, miR-21, miR-155, and miR-221 were able to differentiate BC patients from controls with an area under curve of 0.871, 0.815 and 0.940 respectively. The highest sensitivity: specificity ratio (%) was noted for miR-221 (92:100) followed by miR-155 (50:100) and miR-21 (100:60). A significantly improved diagnostic accuracy was observed following combined ROC analysis of 3-miRNAs. No significant correlations were noted between expression of miRNAs and clinicopathological features.
In summary, serum miR-21, -155, and -221 panel have the potential to serve as non-invasive diagnostic biomarker option in BC patients thereby assisting in improved clinical care.