MicroRNA-223 and microRNA-92a in stool and plasma samples act as complementary biomarkers to increase colorectal cancer detection.
MicroRNA-223 and microRNA-92a in stool and plasma samples act as complementary biomarkers to increase colorectal cancer detection.
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DOI：
10.18632/oncotarget.7119
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Chan EC
中科院分区：
文献类型：
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作者：
Chang PY;Chen CC;Chang YS;Tsai WS;You JF;Lin GP;Chen TW;Chen JS;Chan EC
循环miRNAs的异常水平是早期发现结直肠癌(CRC)的潜在生物标志物。然而，以前没有系统的研究检查过同一患者不同类型标本中的miRNAs，以评估其临床应用价值。在这项研究中，我们从2012年前发表的CRC450篇文章中收集了信息，并选择了46个最常报道的与∼相关的miRNAs作为候选。然后，我们建立了46-miRNA多重RT-qPCR方法，并有效地检测了两种临床可获得的样本：粪便潜血试验和EDTA血浆。共有62份组织、447份粪便和398份血浆样本来自结直肠癌患者和健康对照。62例结直肠癌患者的配对肿瘤组织、粪便和血浆样本中可检测到的miRNAs具有良好的相关性。以62例结直肠癌患者和62例健康对照为训练组，分别有5例和11例差异表达的miRNAs在粪便和血浆中获得了大于0.7的ROC曲线下面积。选择的miRNAs随后以剩余的登记样本作为测试队列进行验证；粪便中的4个miRNAs和血浆中的6个miRNAs对结直肠癌患者保持了识别能力。在检验互补效应后，联合检测粪便和血浆标本中常见的miR-223和miR-92a，对结直肠癌诊断的敏感度和特异度分别为96.8%和75%(AuC=0.907)。这些结果使我们能够在两种类型的结直肠癌临床标本中建立双miRNA生物签名，并具有高灵敏度的结直肠癌检测。
Aberrant levels of circulating miRNAs are potential biomarkers for the early detection of colorectal cancer (CRC). However, no previous systematic study has examined miRNAs in various specimen types from the same patient to evaluate their clinical utility. In this study, we compiled information from ∼450 articles published before 2012, and selected the 46 most frequently reported CRC-related miRNAs as candidates. We then established a 46-miRNA multiplex RT-qPCR method, and efficiently examined two clinically accessible samples: stool from fecal occult blood test and EDTA plasma. A total of 62 tissue, 447 stool, and 398 plasma samples were collected from CRC patients and healthy controls. Good correlations of detectable miRNAs were noticed in paired tumor tissues, stool, and plasma samples of 62 CRC patients. Using these 62 CRC patients and 62 matched healthy controls as the training set, 5 and 11 differentially expressed miRNAs achieved the area under the ROC curve (AUC) greater than 0.7 in stool and plasma samples, respectively. The selected miRNAs was subsequently validated using the remaining enrolled samples as the test cohort; 4 miRNAs in stool and 6 miRNAs in plasma were maintained discriminating powers for CRC patients. After examining the complementary effect, combined analysis of miR-223 and miR-92a, which were commonly present in stool and plasma samples, yielded the highest sensitivity of 96.8% and the specificity of 75% for CRC (AUC = 0.907). These results allowed us to establish a two-miRNA biosignature in two types of CRC clinical specimens with a high sensitivity for CRC detection.