Department of Pathology, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD 21231, USA.
Clin Cancer Res. 2013 Jul 1;19(13):3600-10. doi: 10.1158/1078-0432.CCR-12-3092. Epub 2013 May 22.
Our goal was to identify circulating micro RNA (miRNA) levels that could distinguish patients with low-stage pancreatic cancer from healthy and disease controls.
We measured 735 miRNAs in pancreatic cancer case and control sera by QRTPCR using TaqMan MicroRNA Arrays. After array analysis, we selected 18 miRNA candidates for validation in an independent set of cases and control samples.
Of the significantly elevated circulating miRNAs in patients with pancreatic cancer compared with controls, miR-1290 had the best diagnostic performance: receiver operating characteristic (ROC) analysis on miR-1290 serum level yielded curve areas (AUC) of 0.96 [95% confidence interval (CI), 0.91-1.00], 0.81 (0.71-0.91), and 0.80 (0.67-0.93), for subjects with pancreatic cancer (n = 41) relative to healthy controls (n = 19), subjects with chronic pancreatitis (n = 35), and pancreatic neuroendocrine tumors (n = 18), respectively. Serum miR-1290 levels were also significantly higher than healthy controls among patients with intraductal papillary mucinous neoplasm (IPMN; n = 20; AUC = 0.76, 0.61-0.91). Serum miR-1290 levels distinguished patients with low-stage pancreatic cancer from controls better than CA19-9 levels, and like CA19-9, higher miR-1290 levels predicted poorer outcome among patients undergoing pancreaticoduodenectomy. Greater numbers of miR-1290 transcripts were detected by FISH in primary pancreatic cancer and IPMN than normal pancreatic duct cells. miR-1290 influenced in vitro pancreatic cancer cell proliferation and invasive ability. Several other circulating miRNAs distinguished sera of patients with pancreatic cancer from those of healthy controls with AUCs >0.7, including miR-24, miR-134, miR-146a, miR-378, miR-484, miR-628-3p, and miR-1825.
The detection of elevated circulating miR-1290 has the potential to improve the early detection of pancreatic cancer.
我们的目标是鉴定出可区分低分期胰腺癌患者与健康者和疾病对照者的循环 microRNA（miRNA）水平。
我们通过 TaqMan MicroRNA Arrays 用 QRTPCR 测量了胰腺癌病例和对照者血清中的 735 种 miRNA。在阵列分析后，我们选择了 18 个 miRNA 候选者，用于在独立的病例和对照样本中进行验证。
与对照组相比，患有胰腺癌的患者中明显升高的循环 miRNA 中，miR-1290 的诊断性能最佳：miR-1290 血清水平的接收者操作特征（ROC）分析产生了相对于健康对照（n=19）、慢性胰腺炎患者（n=35）和胰腺神经内分泌肿瘤患者（n=18），患有胰腺癌的受试者（n=41）的曲线下面积（AUC）分别为 0.96 [95%置信区间（CI），0.91-1.00]、0.81（0.71-0.91）和 0.80（0.67-0.93）。在患有胰管内乳头状黏液性肿瘤（IPMN；n=20）的患者中，血清 miR-1290 水平也明显高于健康对照者（AUC=0.76，0.61-0.91）。血清 miR-1290 水平比 CA19-9 水平更好地区分了低分期胰腺癌患者与对照组，并且与 CA19-9 一样，较高的 miR-1290 水平预示着接受胰十二指肠切除术的患者预后更差。通过 FISH 在原发性胰腺癌和 IPMN 中检测到的 miR-1290 转录本数量多于正常胰管细胞。miR-1290 影响体外胰腺癌细胞的增殖和侵袭能力。其他几种循环 miRNA 的 AUC 值大于 0.7，可将胰腺癌患者的血清与健康对照者区分开来，包括 miR-24、miR-134、miR-146a、miR-378、miR-484、miR-628-3p 和 miR-1825。
检测升高的循环 miR-1290 有可能改善胰腺癌的早期检测。
