Objective: MicroRNAs (miRNAs) have been shown to anticipate great cancer diagnostic potential. We investigated whether plasma miRNAs could 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 individuals as controls. (ii) Marker selection and validation by real-time quantitative RT-PCR on a small set of plasma. (iii) Independent validation on a large set of plasma from 90 CRC patients, 20 gastric cancer patients, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls.
Results: Of the panel of 95 miRNAs analyzed, 5 miRNAs were up-regulated both in plasma and tissue samples. All the 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 (relative expression in comparison to RNU6B snRNA), the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects.
Conclusion: MiR-92 is significantly elevated in plasma of CRC patients and can be a potential noninvasive molecular marker for CRC screening.