MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease.
MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease.
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DOI：
10.1158/1940-6207.capr-09-0094
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Sen S
中科院分区：
文献类型：
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作者：
Wang J;Chen J;Chang P;LeBlanc A;Li D;Abbruzzesse JL;Frazier ML;Killary AM;Sen S
为了降低胰腺癌的高发病率和死亡率，迫切需要开发微创生物标志物检测方法，以进行胰腺癌的早期检测和有效的临床管理。我们假设，如果在血浆中检测到胰腺腺癌组织中异常表达的microRNAs (miRNAs)，那么这些microRNAs的血浆谱分析可能作为这种恶性肿瘤的微创早期检测生物标志物分析。通过使用改进的方案从肝素治疗的血液中分离和量化血浆miRNA，我们发现血浆miRNA分析可以区分胰腺腺癌患者和健康对照。我们已经分析了四个mirna， miR-21, miR-210， miR-155和miR-196a，它们都与胰腺癌的发展有关，并且已证实或预测的靶基因参与了关键的癌症相关细胞通路。其中，miR-155最近被确定为早期胰腺肿瘤的候选生物标志物，而miR196a的表达升高已被证明与疾病的进展平行。结果显示，在分析这四种mirna的血浆水平时，灵敏度为64%，特异性为89%。采用留一交叉验证方案和不采用留一交叉验证方案时，受试者工作特征曲线下面积分别为0.82和0.78。这些观察结果，虽然目前是一个“原理证明”的发现，但证明了将血浆miRNA分析作为一种敏感和特异性的基于血液的胰腺癌生物标志物检测的可行性，并有可能在未来进一步改进，转化为临床应用。
Development of minimally invasive biomarker assays for early detection and effective clinical management of pancreatic cancer is urgently needed to reduce high morbidity and mortality associated with this malignancy. We hypothesized that if aberrantly expressing microRNAs (miRNAs) in pancreatic adenocarcinoma tissues are detected in blood plasma then plasma profiling of these miRNAs might serve as a minimally invasive early detection biomarker assay for this malignancy. By utilizing a modified protocol to isolate and quantify plasma miRNAs from heparin treated blood we show that miRNA profiling in plasma can differentiate pancreatic adenocarcinoma patients from healthy controls. We have profiled four miRNAs, miR-21, miR-210, miR-155 and miR-196a, all implicated in the development of pancreatic cancer with either proven or predicted target genes involved in critical cancer associated cellular pathways. Of these, miR-155 has recently been identified as a candidate biomarker of early pancreatic neoplasia while elevated expression of miR196a has been shown to parallel progression of disease. The results revealed a sensitivity of 64% and a specificity of 89% with the analyses of plasma levels for this panel of four miRNAs. The area under the receiver operating characteristic (ROC) curve were estimated at 0.82 and 0.78 without and with leave one out cross validation scheme respectively. These observations, although a “proof of principle” finding at this time, demonstrate the feasibility of developing plasma miRNA profiling as a sensitive and specific blood based biomarker assay for pancreatic cancer that has the potential of translation to the clinic with additional improvements in the future.