Permuth-Wey Jennifer, Chen Dung-Tsa, Fulp William J, Yoder Sean J, Zhang Yonghong, Georgeades Christina, Husain Kazim, Centeno Barbara Ann, Magliocco Anthony M, Coppola Domenico, Malafa Mokenge
Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida. Department of Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
Departments of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida.
Cancer Prev Res (Phila). 2015 Sep;8(9):826-34. doi: 10.1158/1940-6207.CAPR-15-0094.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous neoplasms (IPMN) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of miRNAs 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 preoperative 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% confidence interval (CI), 62.3-86.5, P = 0.002]. The signature contained novel miRNAs and miRNAs previously implicated in pancreatic carcinogenesis that had 2- to 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 the preoperative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment.
胰腺导管腺癌（PDAC）是全球最致命的癌症之一，部分原因是缺乏在早期可手术阶段检测该疾病的方法。存在一种称为导管内乳头状黏液性肿瘤（IPMN）的非侵入性PDAC前体，需要采取策略来辅助其正确诊断和管理。数据支持了微小RNA（miRNA）在IPMN进展为恶性肿瘤过程中的重要性，我们推测miRNA可能从IPMN组织中释放并在血液中被检测到。我们的主要目标是测量经病理证实的IPMN患者和健康对照者术前存档血浆中miRNA的丰度，并发现能够区分IPMN患者与对照以及“恶性”和“良性”IPMN的血浆miRNA。使用新型nCounter技术评估800种miRNA，我们发现一个由30种miRNA组成的特征图谱能够区分42例IPMN病例和24例对照（曲线下面积[AUC]=74.4；95%置信区间[CI]，62.3 - 86.5，P = 0.002）。该特征图谱包含新的miRNA以及先前与胰腺癌发生相关的miRNA，其在病例中的表达比对照高2至4倍。我们还生成了一个由5种miRNA组成的特征图谱，可区分21例恶性（高级别发育异常和浸润性癌）和21例良性（低级别和中级别发育异常）IPMN（AUC = 73.2；95% CI，57.6 - 73.2，P = 0.005），并且表明IPMN患者的配对血浆和组织样本可具有不同的miRNA表达谱。这项研究表明，使用新的具有成本效益的技术开发基于miRNA的血液检测方法，以辅助术前识别需要切除的恶性IPMN，同时使良性IPMN个体避免过度治疗相关的发病率，是可行的。
