Plasma MiR-21 A Potential Diagnostic Marker of Colorectal Cancer
Plasma MiR-21 A Potential Diagnostic Marker of Colorectal Cancer
复制标题
DOI：
10.1097/sla.0b013e318265bd6f
复制
发表时间：
2012-09-01
影响因子：
9
通讯作者：
Galandiuk, Susan
中科院分区：
文献类型：
--
作者：
Kanaan, Ziad;Rai, Shesh N.;Galandiuk, Susan
目的：本研究的主要目的是探讨循环microRNA（miRNAs）作为散发性结直肠癌（CRC）生物标志物的潜在用途。背景：CRC是导致死亡的主要原因，如果早期发现是可以治愈的。对于准确的、非侵入性的CRC生物标志物存在未满足的需求。MiRNA是调节基因表达的非蛋白质编码RNA，在CRC的发展中发挥作用。方法：使用微流控阵列技术（Applied Biosystems）在30名CRC患者的“训练”组中测定了380种miRNA的水平，从这些患者中收集了癌症和邻近的正常组织。然后在第二个盲法“测试”组中验证4种失调最严重的miRNA（P < 0.05，错误发现率（FDR）：10%），该组由16名CRC患者组成，从这些患者中收集癌症和正常邻近组织。然后在由30名CRC患者和30名未患CRC的个体组成的血浆“测试”组中评估经验证的组织miRNA。然后在一个独立的新的血浆测试组中验证最失调的组织miRNAs，该测试组由20名CRC患者和20名年龄、性别和种族匹配的未患CRC.Results的受试者组成：在组织“训练”组中，380种miRNAs中有19种在CRC组织中失调（P < 0.05，FDR：10%）。在我们的“测试”组中，2种上调最多的（miR-31; miR-135 b）和下调最多的（miR-1; miR-133 a）miRNA以100%的灵敏度和80%的特异性鉴定了CRC。MiR-31在III期和IV期的表达高于I期和II期（P < 0.05）。在“血浆”组中，miR-21以90%的特异性和灵敏度区分CRC患者和对照组。血浆miR-21需要在更大的队列中进行研究。作为CRC的血浆生物标志物，它似乎具有独特的前景。
Objectives: The main objective of this study was to investigate the potential use of circulating microRNAs ( miRNAs) as biomarkers of sporadic colorectal cancer (CRC).Background: CRC, a leading cause of death, is curable if detected early. There is an unmet need for an accurate, noninvasive biomarker of CRC. MiRNAs are non-protein-coding RNAs regulating gene expression that play a role in CRC development.Methods: Levels of 380 miRNAs were determined using microfluidic array technology (Applied Biosystems) in a "training" set of 30 CRC patients from whom cancer and adjacent normal tissue were collected. The 4 most dysregulated miRNAs (P < 0.05, false discovery rate (FDR): 10%) were then validated in a second blinded "test" set of 16 CRC patients from whom cancer and normal adjacent tissue had been collected. Validated tissue miRNAs were then evaluated in a plasma "test" set consisting of 30 CRC patients and 30 individuals without CRC. The most dysregulated tissue miRNAs were then validated in an independent new plasma test set consisting of 20 CRC patients with 20 age-, -, and race-matched subjects without CRC.Results: Nineteen of 380 miRNAs were dysregulated in CRC tissue in the tissue "training" set (P < 0.05, FDR: 10%). The 2 most upregulated (miR-31; miR-135b) and most downregulated (miR-1; miR-133a) miRNAs identified CRC in our "test" set with 100% sensitivity and 80% specificity. MiR-31 was more upregulated in stages III and IV compared with stages I and II (P < 0.05). In the "plasma" group, miR-21 differentiated CRC patients from controls with 90% specificity and sensitivity.Conclusions: Plasma miRNAs provide reliable and noninvasive markers for CRC. Plasma miR-21 warrants study in larger cohorts. It seems uniquely promising as a plasma biomarker for CRC.