Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
PLoS One. 2013 May 14;8(5):e62880. doi: 10.1371/journal.pone.0062880. Print 2013.
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers. Circulating microRNAs (miRNAs) have been suggested as potentially promising markers for early detection of CRC. We aimed to identify and evaluate a panel of miRNAs that might be suitable for CRC early detection.
MiRNAs were profiled by TaqMan MicroRNA Array and screened for differential expression in 5 pools of plasma samples of CRC patients (N = 50) and 5 pools of neoplasm-free controls (N = 50). Additional miRNAs were selected from a literature review. Identified candidates were evaluated in independent validation samples with respect to discrimination of CRC patients (N = 80) or advanced adenoma patients (N = 50) and neoplasm-free controls (N = 194). Diagnostic performance of the panel of miRNAs was assessed by multiple logistic regression, using bootstrap analysis to correct for over-optimism.
Five miRNAs identified to be differentially expressed from TaqMan MicroRNA Array (miR-29a, -106b, -133a, -342-3p, -532-3p), and seven miRNAs reported to be differentially expressed in the literature (miR-18a, -20a, -21, -92a, -143, -145, -181b) were selected for validation. Nine of the twelve miRNAs (miR-18a, -20a, -21, -29a, -92a, -106b, -133a, -143, -145) were found to be differentially expressed in CRC patients and controls in the validation samples. The optimism-corrected area under the curve was 0.745 (95% confidence interval: 0.708-0.846). None of the selected miRNAs showed significant differential expression between advanced adenoma patients and neoplasm-free controls.
The identified panel of miRNAs could be of potential use in the development of a multi-marker blood based test for early detection of CRC.
The study underscores the high potential of plasma miRNAs for the improvement of current offers of non-invasive CRC screening.
结直肠癌（CRC）是最常见的癌症之一。循环 microRNAs（miRNAs）已被认为是 CRC 早期检测的潜在有希望的标志物。我们旨在鉴定和评估一组可能适合 CRC 早期检测的 miRNA。
通过 TaqMan MicroRNA 阵列对 miRNA 进行分析，并对 5 例 CRC 患者（N=50）和 5 例无肿瘤对照（N=50）的血浆样本进行差异表达筛选。从文献综述中选择了其他 miRNA。从独立验证样本中评估了鉴定出的候选物，以区分 CRC 患者（N=80）或高级腺瘤患者（N=50）和无肿瘤对照（N=194）。使用 bootstrap 分析校正过度乐观，通过多元逻辑回归评估 miRNA 组的诊断性能。
从 TaqMan MicroRNA 阵列中鉴定出 5 个差异表达的 miRNA（miR-29a、-106b、-133a、-342-3p、-532-3p），并从文献中报道的 7 个差异表达的 miRNA（miR-18a、-20a、-21、-92a、-143、-145、-181b）中选择了 7 个 miRNA 进行验证。在验证样本中，12 个 miRNA 中有 9 个（miR-18a、-20a、-21、-29a、-92a、-106b、-133a、-143、-145）在 CRC 患者和对照组中存在差异表达。校正后的曲线下面积为 0.745（95%置信区间：0.708-0.846）。在高级腺瘤患者和无肿瘤对照之间，没有选择的 miRNA 显示出显著的差异表达。
鉴定的 miRNA 组可能有助于开发基于多标志物的血液检测，用于 CRC 的早期检测。
该研究强调了血浆 miRNAs 在改善当前非侵入性 CRC 筛查方法方面的巨大潜力。
