Differential expression of microRNAs in plasma of colorectal cancer patients: a potential marker for colorectal cancer screening

Abstract

OBJECTIVE: MicroRNAs (miRNA), a class of small non-coding RNAs, play important roles in cancers and have been shown to have great cancer diagnostic potential. Since cell-free miRNAs are recently detected in the plasma and serum, we investigated whether plasma miRNAs enable to discriminate patients with and without colorectal cancer (CRC). METHODS: This study was divided into three phases: (i) Marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of 5 CRC patients, along with plasma from 5 healthy controls. (ii) miRNA marker selection and validation by real-time quantitative RT-PCR on plasma from 25 CRC and 20 healthy controls. (iii) Validation on an independent set of plasma from 90 CRC patients, 20 gastric cancers, 20 inflammatory bowel disease and 50 healthy controls. RESULTS: Of the panel of 95 miRNAs analyzed, 5 miRNAs were up-regulated both in plasma and tissue samples. All 5 miRNAs were validated on the plasma of 25 CRC patients and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in CRC patients (p<0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 CRC patients (p<0.05). Further validation with an independent set of plasma samples (n=180) indicated that miR-92 differentiates CRC from gastric cancer, IBD and normal subjects. This marker yielded a receiver operating characteristic curve area of 88.5%. At a cutoff of 240, the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects. Conclusions: Our findings demonstrated that plasma miRNAs have great potential for CRC screening. This opens up a new class of molecular markers for CRC diagnosis.