Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Int J Cancer. 2015 Jan 1;136(1):152-61. doi: 10.1002/ijc.28136. Epub 2014 Apr 25.
Colonoscopy remains the standard screening method for detecting colorectal cancer (CRC) at an early stage. However, many people avoid having a colonoscopy because of the fear for its potential complications. Our study aimed to identify plasma microRNAs for preliminarily screening CRC in general population, so that some unnecessary colonoscopies can be avoided. We investigated plasma microRNA expression in three independent cohorts including the discovery (n = 80), training (n = 112), and validation (n = 49) phases recruited at two medical centers. Microarrays were used for screening 723 microRNAs in 80 plasma samples to identify candidate microRNAs. Quantitative reverse-transcriptase PCR was performed on the 161 training and validation plasma samples to evaluate the candidate microRNAs discovered from microarrays. A logistic regression model was constructed based on the training cohort and then verified by using the validation dataset. Area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified a panel of miR-409-3p, miR-7, and miR-93 that yielded high diagnostic accuracy in discriminating CRC from healthy group (AUC: 0.866 and 0.897 for training and validation dataset, respectively). Moreover, the diagnostic performance of the microRNA panel persisted in nonmetastasis CRC stages (Dukes' A-B, AUC: 0.809 and 0.892 for training and validation dataset, respectively) and in metastasis CRC stages (Dukes' C-D, AUC: 0.917 and 0.865 for training and validation dataset, respectively). In conclusion, our study reveals a plasma microRNA panel that has potential clinical value in early CRC detection and would play a critical role on preliminarily screening CRC in general population.
结肠镜检查仍然是检测结直肠癌(CRC)早期的标准筛查方法。然而,由于担心其潜在并发症,许多人避免进行结肠镜检查。我们的研究旨在鉴定用于普通人群结直肠癌初步筛查的血浆 microRNA,从而避免一些不必要的结肠镜检查。我们在两个医疗中心招募的三个独立队列(发现队列(n=80)、训练队列(n=112)和验证队列(n=49))中研究了血浆 microRNA 的表达。使用 microarray 筛选了 80 个血浆样本中的 723 个 microRNA,以鉴定候选 microRNA。在 161 个训练和验证血浆样本中进行了定量逆转录酶 PCR,以评估从 microarray 中发现的候选 microRNA。基于训练队列构建了逻辑回归模型,然后使用验证数据集进行验证。使用接收器工作特征曲线下的面积(AUC)评估诊断准确性。我们鉴定了一组 miR-409-3p、miR-7 和 miR-93,它们在区分 CRC 与健康组方面具有较高的诊断准确性(AUC:训练和验证数据集分别为 0.866 和 0.897)。此外,microRNA 组在非转移 CRC 阶段(Dukes' A-B,AUC:训练和验证数据集分别为 0.809 和 0.892)和转移 CRC 阶段(Dukes' C-D,AUC:训练和验证数据集分别为 0.917 和 0.865)中具有诊断性能。总之,我们的研究揭示了一种具有潜在临床价值的血浆 microRNA 组,可用于早期 CRC 检测,并在普通人群中结直肠癌的初步筛查中发挥关键作用。