The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs whose expression changes are associated with cancer development and invasion. We hypothesized that miR-10b and miR-373, which are increased in lymphatic metastatic tissues, could be directly assayed in the plasma and used to detect the lymph node status of breast cancer patients. Between November 2009 and January 2012, 35 breast ductal carcinoma patients with lymph node metastasis (N patients), 25 ductal carcinoma patients without lymph node metastasis (N(0) patients), and ten healthy female donors were enrolled in the study. Circulating miR-10b and miR-373 were determined in preoperative plasma samples by reverse transcription quantitative real-time PCR assay. In preliminary tests, the plasma levels of circulating miR-10b and miR-373 were found to be significantly higher in ten breast cancer patients with lymph node metastasis compared to ten N(0) patients and ten normal donors (P < 0.01). On validation analysis, the median value level of miR-10b in the 35 N patients was 4.44-fold (P < 0.01) increased, and miR-373 was 4.38-fold (P < 0.01) increased in comparison to the 25 N(0) patients. MiR-10b was used for differentiation of N patients from N(0) patients; the odds ratio was 2.19, and the value of the area under the receiver-operating curve (AUC) was 0.80, with sensitivity of 71% and specificity of 72%. For miR-373, the odds ratio was 2.62, and the AUC was 0.84, with sensitivity of 68% and specificity of 89%. A combination of the two circulating miRNAs further enhanced the sensitivity to 72% and the specificity to 94.3%. Our data suggest that circulating miRNA-10b and miRNA-373 are potential biomarkers for detecting the lymph node status of breast cancer.