Ng E K O, Chong W W S, Jin H, Lam E K Y, Shin V Y, Yu J, Poon T C W, Ng S S M, Sung J J Y
Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
Gut. 2009 Oct;58(10):1375-81. doi: 10.1136/gut.2008.167817. Epub 2009 Feb 6.
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).
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.
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.
MiR-92 is significantly elevated in plasma of patients with CRC and can be a potential non-invasive molecular marker for CRC screening.
微小RNA（miRNA）已显示出在癌症诊断中具有巨大潜力。我们研究了血浆miRNA是否能够区分结直肠癌（CRC）患者和非CRC患者。
本研究分为三个阶段：（1）使用基于实时PCR的miRNA分析技术，对5例CRC患者的血浆、相应癌组织及相邻非癌结肠组织进行分析，并以5名健康个体的血浆作为对照，以发现标志物；（2）通过对一小部分血浆进行实时定量RT-PCR来选择和验证标志物；（3）对来自90例CRC患者、20例胃癌患者、20例炎症性肠病（IBD）患者和50名健康对照的大量血浆进行独立验证。
在所分析的95种miRNA中，有5种在血浆和组织样本中均上调。这5种miRNA在25例CRC患者和20名健康对照的血浆中均得到验证。miR-17-3p和miR-92在CRC患者中均显著升高（p<0.0005）。10例CRC患者术后这些标志物的血浆水平显著降低（p<0.05）。使用另一组独立的血浆样本（n = 180）进一步验证表明，miR-92可区分CRC与胃癌、IBD和正常受试者。该标志物的受试者工作特征曲线面积为88.5%。在截断值为240（相对于RNU6B snRNA的相对表达）时，区分CRC与对照受试者的灵敏度为89%，特异性为70%。
miR-92在CRC患者血浆中显著升高，可能成为CRC筛查的潜在非侵入性分子标志物。
