Xu Jianwei, Cao Zhe, Liu Wenjing, You Lei, Zhou Li, Wang Chunyou, Lou Wenhui, Sun Bei, Miao Yi, Liu Xubao, Zhang Taiping, Zhao Yupei
*Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China†Pancreatic Disease Institute, Department of General Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China‡Departments of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China§Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China¶Department of General Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China||Department of Hepatopancreatobiliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Ann Surg. 2016 Jun;263(6):1173-9. doi: 10.1097/SLA.0000000000001345.
To identify plasma microRNA (miRNA) markers of pancreatic cancer (PC).
Accurate pretreatment diagnosis of PC remains challenging, whether plasma miRNAs could be used as biomarkers in PC remains unknown.
In this multiphase multicenter study, peripheral blood samples were obtained preoperatively in 3 phases: the discovery phase [7 patients with PC, 6 patients with chronic pancreatitis (CP), and 5 healthy volunteers (N)], the preliminary validation phase (29 patients with PC, 16 patients with CP, and 31 N), and the large sample validation phase (156 patients with PC, 65 N, 57 patients with CP, 27 patients with pancreatic neuroendocrine tumors, and 58 patients with other pancreatic tumors). The diagnostic values of the miRNAs were assessed and compared with cancer antigen 19-9 (CA19-9).
The discovery phase demonstrated that 29 miRNAs were dysregulated in the patients with PC compared with the controls. In the preliminary validation phase, 13 miRNAs were shown to be dysregulated in the patients with PC and were selected for validation in a multicenter trial. MiR-486-5p exhibited diagnostic value in discriminating patients with PC from normal subjects or patients with CP, with area under the curve values of 0.861 and 0.707, respectively. MiR-938 exhibited diagnostic value in differentiating patients with PC from those with CP, pancreatic neuroendocrine tumors, and patients with other pancreatic tumors, with area under the curve values of 0.693, 0.660, and 0.618, respectively. In addition, we demonstrated that the value of miR-486-5p in discriminating patients with PC from normal subjects or patients with CP was comparable with that of CA19-9 (P = 0.602 and P = 0.230).
This study identified several plasma miRNAs potentially suitable for distinguishing patients with PC from normal subjects or patients with other pancreatic tumors.
鉴定胰腺癌(PC)的血浆微小RNA(miRNA)标志物。
PC的准确术前诊断仍然具有挑战性,血浆miRNAs是否可作为PC的生物标志物尚不清楚。
在这项多阶段多中心研究中,在术前3个阶段采集外周血样本:发现阶段[7例PC患者、6例慢性胰腺炎(CP)患者和5名健康志愿者(N)]、初步验证阶段(29例PC患者、16例CP患者和31名N)以及大样本验证阶段(156例PC患者、65名N、57例CP患者、27例胰腺神经内分泌肿瘤患者和58例其他胰腺肿瘤患者)。评估miRNAs的诊断价值并与癌抗原19-9(CA19-9)进行比较。
发现阶段表明,与对照组相比,29种miRNAs在PC患者中表达失调。在初步验证阶段,13种miRNAs在PC患者中显示出表达失调,并被选入多中心试验进行验证。MiR-486-5p在区分PC患者与正常受试者或CP患者方面具有诊断价值,曲线下面积值分别为0.861和0.707。MiR-938在区分PC患者与CP患者、胰腺神经内分泌肿瘤患者和其他胰腺肿瘤患者方面具有诊断价值,曲线下面积值分别为0.693、0.660和0.618。此外,我们证明了MiR-486-5p在区分PC患者与正常受试者或CP患者方面的价值与CA19-9相当(P = 0.602和P = 0.230)。
本研究鉴定了几种可能适用于区分PC患者与正常受试者或其他胰腺肿瘤患者的血浆miRNAs。