Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening
- E K O Ng1,
- W W S Chong1,2,
- H Jin1,
- E K Y Lam1,
- V Y Shin1,2,
- J Yu1,2,
- T C W Poon1,2,
- S S M Ng1,3,
- J J Y Sung1,2
- 1Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, China
- 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, China
- 3Department of Surgery, The Chinese University of Hong Kong, China
- Correspondence to Dr J J Y Sung, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China; joesung{at}cuhk.edu.hk
- Revised 6 December 2008
- Accepted 6 January 2009
- Published Online First 6 February 2009
Abstract
Objective: MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer (CRC).
Methods: This study was divided into three phases: (1) marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of five patients with CRC, along with plasma from five healthy individuals as controls; (2) marker selection and validation by real-time quantitative RT-PCR on a small set of plasma; and (3) independent validation on a large set of plasma from 90 patients with CRC, 20 patients with gastric cancer, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls.
Results: Of the panel of 95 miRNAs analysed, five were upregulated both in plasma and tissue samples. All the five miRNAs were validated on the plasma of 25 patients with CRC and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in the patients with CRC (p<0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 patients with CRC (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 cut-off 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 patients with CRC and can be a potential non-invasive molecular marker for CRC screening.
Footnotes
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Funding The project was supported by the CUHK Direct Grant No. 2041342 and Research Funding from the Institute of Digestive Disease and the Li Ka Shing Institute of Health Science, the Chinese University of Hong Kong.
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Competing interests None.
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Provenance and Peer review Not commissioned; externally peer reviewed.
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See Commentary, p 1318
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Ethics approval This project was approved by the Joint CUHK-NTE Clinical Research Ethics Committee, Hong Kong, on 27 February 2008.
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‣ Two supplementary tables and a figure are published online only at http://gut.bmj.com/content/vol58/issue10
