Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas.
Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas.
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DOI：
10.1158/1940-6207.capr-15-0094
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Malafa M
中科院分区：
文献类型：
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作者：
Permuth-Wey J;Chen DT;Fulp WJ;Yoder SJ;Zhang Y;Georgeades C;Husain K;Centeno BA;Magliocco AM;Coppola D;Malafa M
胰腺导管腺癌(PDAC)是世界上最致命的癌症之一，部分原因是缺乏在早期可手术阶段发现疾病的方法。存在称为导管内乳头状黏液性肿瘤(IPMN)的非侵袭性PDAC前体，需要采取策略来帮助其正确诊断和处理。数据支持miRNAs在IPMN向恶性进展过程中的重要性，我们假设miRNAs可能从IPMN组织中脱落并在血液中检测到。我们的主要目标是测量手术前存档的血浆中miRNAs的丰度，这些miRNAs来自经病理证实的IPMN患者和健康对照组，并发现区分IPMN患者和对照组以及“恶性”和“良性”IPMN的血浆miRNAs。使用新的NCounter技术™评估800miRNA，我们发现30-miRNA特征区分了42例IPMN和24例对照(曲线下面积=74.495%CI：62.386.5，p=0.002)。该签名包含新的miRNAs和先前与胰腺癌发生有关的miRNAs，它们在病例中的表达是对照组的2-4倍。我们还生成了一个5-miRNA签名，它可以区分21个恶性(高度不典型增生和浸润性癌)和21个良性(低和中度不典型增生)IPMN(AUC=73.2(95%CI：57.673.2，p=0.005))，并显示来自IPMN患者的配对血浆和组织样本可以有不同的miRNA表达谱。这项研究建议使用新的经济有效的技术来开发一种基于miRNA的血液测试的可行性，以帮助术前识别需要切除的恶性IPMN，同时避免良性IPMN患者与过度治疗相关的发病率。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers world-wide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous neoplasms (IPMNs) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of mi(cro)RNAs in the progression of IPMNs to malignancy, and we hypothesized that miRNAs may be shed from IPMN tissues and detected in blood. Our primary goals were to measure the abundance of miRNAs in archived pre-operative plasma from individuals with pathologically-confirmed IPMNs and healthy controls and discover plasma miRNAs that distinguish between IPMN patients and controls and between ‘malignant’ and ‘benign’ IPMNs. Using novel nCounter technology™ to evaluate 800 miRNAs, we showed that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls (area underneath the curve (AUC)= 74.4 (95% CI:62.3-86.5, p=0.002). The signature contained novel miRNAs and miRNAs previously implicated in pancreatic carcinogenesis that had 2-4 fold higher expression in cases than controls. We also generated a 5-miRNA signature that discriminated between 21 malignant (high-grade dysplasia and invasive carcinoma) and 21 benign (low- and moderate-grade dysplasia) IPMNs (AUC=73.2 (95% CI: 57.6-73.2, p=0.005)), and showed that paired plasma and tissue samples from patients with IPMNs can have distinct miRNA expression profiles. This study suggests feasibility of using new cost-effective technology to develop a miRNA-based blood test to aid in pre-operative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment.