Abstract:
microRNAs (miRNAs) play an important role in cancer prognosis. They are
small molecules, approximately 17-25 nucleotides in length, and their high stability in
human serum supports their use as novel diagnostic biomarkers of cancer and other
pathological conditions. In this study, we analyzed the expression patterns of miR-21
and miR-221 in the serum from a total of 100 Egyptian female subjects with breast
cancer, fibroadenoma, and healthy control subjects. Using microarray-based
expression profiling followed by real-time polymerase chain reaction validation, we
compared the levels of the two circulating miRNAs in the serum of patients with
breast cancer (n= 50), fibroadenoma (n= 25), and healthy controls (n= 25). The
miRNA SNORD68 was chosen as the housekeeping endogenous control. We found
that the serum levels of miR-21 and miR-221 were significantly overexpressed in
breast cancer patients compared to normal controls and fibroadenoma patients.
Receiver Operating Characteristic (ROC) curve analysis revealed that miR-21 has
greater potential in discriminating between breast cancer patients and the control
group, while miR-221 has greater potential in discriminating between breast cancer
and fibroadenoma patients. Classification models using k-Nearest Neighbor (kNN),
Naïve Bayes (NB), and Random Forests (RF) were developed using expression levels
of both miR-21 and miR-221. Best classification performance was achieved by NB
Classification models, reaching 91% of correct classification. Furthermore, relative
miR-221 expression was associated with histological tumor grades. Therefore, it may
be concluded that both miR-21 and miR-221 can be used to differentiate between
breast cancer patients and healthy controls, but that the diagnostic accuracy of serum
miR-21 is superior to miR-221 for breast cancer prediction. miR-221 has more
diagnostic power in discriminating between breast cancer and fibroadenoma patients.
The overexpression of miR-221 has been associated with the breast cancer grade. We
also demonstrated that the combined expression of miR-21 and miR-221can be
successfully applied as breast cancer biomarkers.