Identification and clinical implications of circulating microRNAs for estrogen receptor positive breast cancer

Abstract

Background

MicroRNA expression is frequently dysregulated in cancer and it could be used potentially as a disease classifier and a prognostic tool in cancer. It has been reported that the cancer associated specific microRNAs were detected in blood stably. The objective of this study was to discover a panel of circulating microRNAs as potential ER+/HER2- breast cancer biomarkers.

Methods

We compared the levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients with age-matched 5 control subjects by using microarray-based expression profiling followed by real-time quantitative polymerase cycle reaction (RT-qPCR) validation. We evaluated the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer.

Results

We found that 4 microRNAs (miR-1280, miR-1260, miR-1274b, miR-720) were up-regulated in blood from breast cancer patients (P<0.05, constrained by at least two-fold expression change). We evaluated the level of each microRNAs in 40 control subjects, 180 early breast cancer patients (EBC), and 52 metastatic breast cancer patients (MBC). Among those, the levels of miR-1280 significantly increased in breast cancer patients and those were correlated with tumor status (control<<EBC<MBC). Among 37 MBC patients, the levels of miR-1280 were decreasing significantly in patients who responded to the systemic treatment (P<0.001). In addition, patients with decreasing miR-1280 levels showed better survival than those with increasing or stable ones (P<0.058). We confirmed that miR-1280 was not a classic microRNA, but a metabolite of tRNALeu which could be classified as a tRNA - derived fragment.

Conclusions

These findings suggest that a circulating tRNA derived miRNA, miR-1280 is differently expressed in breast cancer patients and it can be used as a potential biomarker for ER positive breast cancer.