Expression Profile of MicroRNAs in Serum: A Fingerprint for Esophageal Squamous Cell Carcinoma
Expression Profile of MicroRNAs in Serum: A Fingerprint for Esophageal Squamous Cell Carcinoma
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血清中 MicroRNA 的表达谱：食管鳞状细胞癌的指纹
DOI：
10.1373/clinchem.2010.147553
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发表时间：
2010-12-01
影响因子：
9.3
通讯作者：
Zhang, Chen-Yu
中科院分区：
文献类型：
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作者：
Zhang, Chunni;Wang, Cheng;Zhang, Chen-Yu
背景：为了降低食管鳞癌的高发病率和病死率，迫切需要敏感和特异的生物标志物来早期发现食管鳞癌。血清microRNAs(MiRNAs)的发现及其在各种疾病患者体内的独特浓度分布使其成为具有吸引力的、用于肿瘤诊断的新型非侵入性生物标志物。在这项研究中，我们调查了ESCC患者的血清miRNA谱，以开发一种新的ESCC诊断生物标志物。方法：采集290例ESCC患者和140名年龄和性别匹配的对照组的血清样本。使用Solexa测序技术对141名患者和40名对照组的血清样本中的miRNAs进行了初步筛选。在训练和验证阶段，采用基于水解探针的茎环定量逆转录聚合酶链式反应(RT-qPCR)检测149例食管鳞癌患者和100名对照组血清样本中所选miRNAs的浓度。结果：Solexa测序结果显示，与对照组相比，ESCC患者血清中25个miRNAs显著上调。RT-qPCR分析确定7个血清miRNAs(miR-10a、miR-22、miR-100、miR-148b、miR-223、miR-133a和miR-127-3p)为ESCC生物标志物。所选miRNA的ROC曲线下面积为0.817-0.949，显著高于癌胚抗原(0.549；P<；0.0005)。更重要的是，这组7个miRNAs清楚地区分了I/II期ESCC患者和对照组。结论：这组7个血清miRNAs有望成为诊断ESCC的一种新的基于血液的生物标志物。(C)2010年美国临床化学协会
BACKGROUND: Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker.METHODS: Serum samples were taken from 290 ESCC patients and 140 age-and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe-based stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls.RESULTS: The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P < 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls.CONCLUSIONS: This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC. (C) 2010 American Association for Clinical Chemistry