Plasma microRNA as a potential marker for breast cancer detection

Abstract

BACKGROUND: Recently, the emergence of small non-protein-coding RNAs, so-called microRNAs (miRNAs), playing important roles in oncogenesis has opened new opportunities for early cancer diagnosis. We have previously shown that microRNAs (miRNAs) in plasma are promising biomarkers for colorectal cancer detection. Here, we investigated whether plasma miRNAs could discriminate patients with and without breast cancer (BC). METHODS: Using TaqMan-based low density miRNA array, miRNAs were profiled from cancerous and adjacent non-cancerous breast tissues, corresponding plasma of 5 BC patients, along with plasma from 5 healthy controls. Marker selection and validation were performed by real-time quantitative RT-PCR on a small set of plasma. Independent set of plasma from 80 BC patients, 20 gastric cancer, 20 lung cancer, 20 colorectal cancer, 20 hepatocellular carcinoma and 50 healthy controls were further validated. RESULTS: Of the panel of 377 miRNAs analyzed, 8 miRNAs (miR-16, miR-21, miR-27a, miR-141, miR-191, miR-200c, miR-210, miR-451) were up-regulated both in plasma and tissue samples of 5 BC patients. All 8 putative miRNA markers were validated on the plasma of 15 BC patients and 15 healthy controls. Only three miRNAs were significantly elevated in this cohort of BC patients (p<0.0005). The plasma levels of the three markers in those 15 BC patients were significantly reduced after surgery (p<0.05). Further validation with an independent set of plasma samples (n=210) indicated that two markers differentiate BC from normal subjects, colorectal cancer, gastric cancer, hepatocellular carcinoma and lung cancer. These two markers yielded a combined receiver operating characteristic curve area of 88.5%, the sensitivity was 92% and the specificity was 72% in discriminating BC from control subjects. CONCLUSIONS: Plasma miRNAs significantly elevated in BC patients are identified. This can be a novel noninvasive molecular marker for BC screening.