A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis
A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis
复制标题
从全基因组血清 microRNA 表达谱中鉴定出的五种 microRNA 特征可作为胃癌诊断的指纹。
DOI：
10.1016/j.ejca.2010.10.025
复制
发表时间：
2011-03-01
影响因子：
8.4
通讯作者：
Zhang, Chen-Yu
中科院分区：
文献类型：
--
作者：
Liu, Rui;Zhang, Chunni;Zhang, Chen-Yu
背景：由于缺乏用于胃癌（GC）检测的非侵入性工具，胃癌患者的预后通常较差。本研究的目的是确定一种血清微小RNA（miRNA）表达谱，可作为胃癌检测的新型诊断生物标志物，并评估其在监测疾病进展中的临床应用。
方法：从164例胃癌患者和127例年龄及性别匹配的无肿瘤对照者中采集血清样本。分别使用来自20例患者和20例对照者的混合血清样本，通过Solexa测序对miRNA表达进行初步筛选。在个体样本中使用基于水解探针的茎环定量逆转录聚合酶链反应（qRT - PCR）对差异表达进行验证，样本分为两个阶段。
结果：Solexa测序结果表明，与对照者相比，胃癌患者中有19种血清miRNA显著上调。qRT - PCR分析进一步确定了五种血清miRNA（miR - 1、miR - 20a、miR - 27a、miR - 34和miR - 423 - 5p）作为胃癌检测的生物标志物。分析结果显示，五种血清miRNA的表达水平与肿瘤分期相关。这五种血清miRNA特征的受试者工作特征（ROC）曲线下面积在两组血清样本中分别为0.879（95%置信区间（CI）0.822 - 0.936）和0.831（95%CI 0.767 - 0.898），明显高于生物标志物癌胚抗原（CEA）（0.503）和糖类抗原19 - 9（CA19 - 9）（0.600）。
结论：我们通过全基因组血清miRNA表达谱确定了用于胃癌诊断的五种miRNA特征。这种基于血清miRNA的生物标志物的表达水平也能指示肿瘤进展阶段。（C）2010爱思唯尔有限公司。保留所有权利。
Background: Prognosis of patients with gastric cancer (GC) is generally poor due to the lack of non-invasive tools for GC detection. The purpose of present study was to identify a serum microRNA (miRNA) expression profile that can serve as a novel diagnostic biomarker for GC detection and to assess its clinical applications in monitoring disease progression.Methods: Serum samples were taken from 164 GC patients and 127 age- and gender-matched tumour-free controls. An initial screening of miRNA expression by Solexa sequencing was performed using serum samples pooled from 20 patients and 20 controls, respectively. Differential expression was validated using hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (qRT-PCR) in individuals samples, the samples were arranged in two phases.Results: The Solexa sequencing results demonstrated that 19 serum miRNAs were markedly upregulated in the GC patients compared to the controls. The qRT-PCR analysis further identified a profile of five serum miRNAs (miR-1, miR-20a, miR-27a, miR-34 and miR-423-5p) as a biomarker for GC detection. The analysis results showed that the expression level of five serum miRNAs was correlated to tumour stage. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.879 (95% confidence interval (CI) 0.822-0.936) and 0.831 (95%. Cl 0.767-0.898) for the two sets of serum samples, respectively, markedly higher than those of the biomarkers carcinoembryonic antigen (CEA) (0.503) and carbohydrate antigen 19-9 (CA19-9) (0.600).Conclusions: We identified five-miRNA signature for GC diagnosis by genome-wide serum miRNA expression profiling. Expression levels of this serum miRNA-based biomarker also indicate tumour progression stages. (C) 2010 Elsevier Ltd. All rights reserved.