A Plasma MicroRNA Panel for Detection of Colorectal Adenomas A Step Toward More Precise Screening for Colorectal Cancer
A Plasma MicroRNA Panel for Detection of Colorectal Adenomas A Step Toward More Precise Screening for Colorectal Cancer
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DOI：
10.1097/sla.0b013e3182a15bcc
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发表时间：
2013-09-01
影响因子：
9
通讯作者：
Galandiuk, Susan
中科院分区：
文献类型：
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作者：
Kanaan, Ziad;Roberts, Henry;Galandiuk, Susan
目的：本研究的主要目的是探讨循环microRNAs （miRNAs）作为结直肠（CR）腺瘤生物标志物的潜在用途。背景：癌前病变如CR腺瘤的检测是降低CR癌（CRC）死亡率的关键。目前迫切需要准确、无创的生物标志物来检测CR腺瘤和CRC。mirna是调节基因表达的非蛋白质编码rna。我们之前的工作研究了CRC患者中5种血浆mirna的失调。按照预期，我们在CR腺瘤和CRC患者中进行了更全面的血浆mirna筛选研究。方法：我们使用微流控阵列技术（Applied BioSystems）在12名健康对照者、9名CR腺瘤患者和20名CRC患者中筛选380个血浆mirna。然后在26名健康对照、16名大腺瘤患者和45名结直肠癌患者的盲法队列中验证了一组最失调的mirna （P < 0.05，错误发现率：5%）。结果：一组8个血浆mirna （miR-532-3p, miR-331, miR-195, miR-17, miR-142-3p, miR-15b， miR-532和miR-652）以高精度将息肉与对照组区分开来[曲线下面积(AUC)= 0.868(95%可信区间[CI]: 0.76-0.98)]。此外，一组3个血浆mirna （miR-431， miR-15b和miR-139-3p）将IV期CRC与对照组区分开来[AUC = 0.896 (95% CI: 0.78-1.0)]。所有结直肠癌与对照组和息肉与所有结直肠癌的miRNA面板的受体工作特征曲线分别显示AUC值为0.829 （95% CI: 0.73-0.93）和0.856 （95% CI: 0.75-0.97）。结论：血浆mirna是可靠的、无创的、廉价的CR腺瘤标志物。这个miRNA小组值得在更大的队列中进行研究。与粪便隐血或内窥镜筛查相比，基于血浆的检测可提供更好的筛查依从性。
Objective: The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of colorectal (CR) adenomas.Background: Detection of precancerous lesions such as CR adenoma is a key to reduce CR cancer (CRC) mortality. There is a great need for accurate, noninvasive biomarkers for detection of CR adenoma and CRC. MiRNAs are non-protein-coding RNAs that regulate gene expression. Our prior work investigated the dysregulation of 5 plasma miRNAs in CRC patients. As intended, we undertook a more comprehensive plasma-miRNA screening study in patients with CR adenoma and CRC.Methods: We screened for 380 plasma-miRNAs using microfluidic array technology (Applied BioSystems) in a screening cohort of 12 healthy controls, 9 patients with CR adenomas, and 20 patients with CRC. A panel of the most dysregulated miRNAs (P < 0.05, False Discovery Rate: 5%) was then validated in a blinded cohort of 26 healthy controls, 16 patients with large adenomas, and 45 patients with CRC.Results: A panel of 8 plasma miRNAs (miR-532-3p, miR-331, miR-195, miR-17, miR-142-3p, miR-15b, miR-532, and miR-652) distinguished polyps from controls with high accuracy [area under curve (AUC)= 0.868 (95% confidence interval [CI]: 0.76-0.98)]. In addition, a panel of 3 plasma miRNAs (miR-431, miR-15b, and miR-139-3p) distinguished Stage IV CRC from controls with an [ AUC = 0.896 (95% CI: 0.78-1.0)]. Receiver-operating-characteristic curves of miRNA panels for all CRC versus controls and polyps versus all CRC showed AUC values of 0.829 (95% CI: 0.73-0.93) and 0.856 (95% CI: 0.75-0.97), respectively.Conclusions: Plasma miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This miRNA panel warrants study in larger cohorts. Plasma-based assays could provide better screening compliance compared to fecal occult blood or endoscopic screening.