MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls
Menée sur des patients atteints d'un cancer du pancréas (41), d'une pancréatite chronique (35) ou d'une tumeur neuroendocrine du pancréas (18) et sur 19 témoins, cette étude suggère l'intérêt de mesurer le niveau circulant du micro-ARN miR-1290 pour la détection précoce d'un cancer du pancréas
Purpose: Our goal was to identify circulating miRNA levels that could distinguish patients with low-stage pancreatic cancer from healthy and disease controls
Experimental Design: 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.
Results: Of the significantly elevated circulating microRNAs in patients with pancreatic cancer compared to 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% CI: 0.91-1.00), 0.81 (0.71-0.91), 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.
Conclusions: The detection of elevated circulating miR-1290 has the potential to improve the early detection of pancreatic cancer.
Clinical Cancer Research , résumé, 2013