Serum MicroRNA Expression Profile as a Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer
Serum MicroRNA Expression Profile as a Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer
复制标题
血清 microRNA 表达谱作为胰腺癌诊断和预后的生物标志物。
DOI：
10.1373/clinchem.2011.172767
复制
发表时间：
2012-03-01
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：
Liu, Rui;Chen, Xi;Zhang, Chen-Yu
背景
由于缺乏特异性生物标志物，胰腺癌（PaC）的检测，特别是在早期阶段，仍然是一个巨大的挑战。我们试图鉴定PaC特异性血清microRNA（miRNA）表达谱，并测试其作为PaC诊断和预后的生物标志物的特异性和敏感性。
方法
我们从197例PaC病例和158例年龄和性别匹配的无癌对照中获得血清样本。我们使用合并的血清样品，通过Illumina测序合成技术筛选差异表达的血清miRNAs，然后对多个阶段中布置的大量样品进行RT-qPCR验证。我们使用风险评分分析来评估血清miRNA谱系统的诊断价值。为了评估基于血清miRNA的生物标志物预测PaC的准确性，我们在77例PaC病例和52例对照中进行了额外的双盲试验，并在55例临床疑似PaC病例中进行了诊断分类。
结果
经过筛选和验证，7个miRNAs在PaC中的表达水平与对照组相比有显著差异。这7种基于miRNA的生物标志物对于区分不同阶段的PaC与无癌症对照具有高灵敏度和特异性，并且还准确区分PaC患者与慢性胰腺炎（CP）患者。在7种miRNAs中，血清中的miR-21水平与总体PaC生存率显著相关。对55例临床疑似PaC患者的诊断准确率为83.6%。
结论
这些数据表明，7种基于miRNA的生物标志物可以作为PaC诊断和预后的新的非侵入性方法。
BACKGROUND
Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC.
METHODS
We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA-based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC.
RESULTS
After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA-based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC.
CONCLUSIONS
These data demonstrate that the 7 miRNA-based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.