Small RNAs are multiple classes of short non-coding RNAs (ncRNAs) that include microRNAs (miRNAs), transfer RNA fragments (tRFs), and other ncRNA fragments that play essential role in gene regulation. Small RNAs exist in blood circulation within extracellular vesicles (EVs), which have been the center of the attention at cell-to-cell communication tools, or bound to proteins or lipid. Recent studies have shown that the expression levels of small RNAs are different between patients with breast cancer (BC) and cancer-free individuals. Thus, circulating small RNAs have attracted as valuable biomarkers for cancer detection.
First, we assessed and the expression level of circulating small RNAs in the serum of BC patients (n = 78) and cancer-free volunteers (control) (n = 72) using next generation sequencer. By comparing those expression level, we identified some small RNAs that have signifficant difference between 2 groups as biomarker candidates for BC detection. We constructed a diagnostic model using some small RNAs from biomarker candidates. To test the possibilities that those candidates are released from cancer cells, we next profiled small RNAs within EVs that isolated from the serum of participants in this study and from breast cancer cells (MCF-7 and MDA-MB-231) and normal epithelial cells (184-h TERT).
Twelve circulating small RNAs that expressed significantly higher in BC patients compared to control were identified, indicating potential biomarkers for BC detection. A diagnostic model using 4 small RNAs including isoforms of miRNAs (isomiRs) and tRFs was. The ROC curve analysis revealed that our model showed a high diagnostic accuracy of AUC 0.945 and achieved discriminating stage 0 BCs from control. Importantly, significantly different expression in serum-EVs was observed in 4 small RNAs between BC patients and control. Furthermore, 4 small RNAs were also observed in EVs derived from cell culture media in breast cancer cells and normal epithelial cells and those expressions were aberrant as the same as those of serum-EVs.
These findings suggests circulating small RNAs in serum serve as potential biomarkers for BC detection that enables to include the molecular movement of cancer cells.
Has not received any funding.
H. Tahara: Advisory / Consultancy: MiRTeL.