Vila-Navarro Elena, Vila-Casadesús Maria, Moreira Leticia, Duran-Sanchon Saray, Sinha Rupal, Ginés Àngels, Fernández-Esparrach Glòria, Miquel Rosa, Cuatrecasas Miriam, Castells Antoni, Lozano Juan José, Gironella Meritxell
*Gastrointestinal & Pancreatic Oncology Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)/Hospital Clínic of Barcelona/ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Catalonia, Spain †Bioinformatics Platform, CIBEREHD/Barcelona, Catalonia, Spain ‡Pathology Department, Hospital Clínic of Barcelona, Barcelona, Catalonia, Spain.
Ann Surg. 2017 Jun;265(6):1226-1234. doi: 10.1097/SLA.0000000000001809.
The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia.
Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates.
Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1-52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2-95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C).
In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively.
miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer.
本研究旨在分析胰腺导管腺癌（PDAC）及其癌前病变导管内乳头状黏液性肿瘤（IPMN）的微小RNA组（miRNome），以寻找基于微小RNA（miRNA）的胰腺肿瘤早期检测新生物标志物。
需要有效的PDAC早期检测方法。miRNA是良好的生物标志物候选物。
从巴塞罗那临床医院的PDAC、IPMN患者或对照个体（C）获取胰腺组织（n = 165）。在18个手术样本（11个PDAC、4个IPMN、3个C）的发现集中使用下一代测序进行生物标志物发现。通过定量逆转录聚合酶链反应在2组不同样本中进行miRNA验证。第1组 - 52个手术样本（24个PDAC、7个IPMN、6个慢性胰腺炎、15个C），第2组 - 95个内镜超声引导下细针穿刺样本（60个PDAC、9个IPMN、26个C）。
总体而言，与C相比，PDAC和IPMN中分别有607个和396个miRNA显著失调。其中，选择了40个在PDAC和IPMN中均普遍过表达的miRNA进行进一步验证。其中，分别在第1组和第2组样本中通过定量逆转录聚合酶链反应证实31个和30个miRNA显著上调。
miRNome分析表明，PDAC和IPMN相对于C具有不同的miRNA谱，两种肿瘤性病变共有大量失调的miRNA。实际上，我们已经鉴定并验证了30个在PDAC和IPMN病变中表达显著增加的miRNA。在内镜超声引导下细针穿刺样本中检测这些miRNA的可行性使其成为胰腺癌早期检测的良好生物标志物候选物。
