The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms

Ann Oncol. 2013 Mar;24(3):734-41. doi: 10.1093/annonc/mds513. Epub 2012 Nov 8.

Abstract

Background: This multicenter study evaluated three candidate microRNAs (miRNAs) (miR-21, miR-155 and miR-101) as potential biomarkers in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.

Patients and methods: miRNA expression was quantified by quantitative RT-PCR in 86 laser-microdissected specimens, including 65 invasive IPMNs, 16 non-invasive IPMNs and 5 normal pancreatic ductal tissues. Univariate and multivariate analyses compared miRNAs and clinical parameters with overall (OS) and disease-free survival (DFS).

Results: miR-21 and miR-155 were up-regulated in invasive IPMNs compared with non-invasive IPMNs, as well as in non-invasive IPMNs compared with normal tissues. Conversely, miR-101 levels were significantly higher in non-invasive IPMNs and normal tissues compared with invasive IPMNs. High levels of miR-21 were associated with worse OS [hazard ratio (HR) = 2.47, 95% confidence interval (CI) = 1.37-5.65, P = 0.0047]. Patients with high-miR-21 expression also had a shorter median DFS (10.9 versus 29.9 months, P = 0.01). Multivariate analysis confirmed miR-21 as independently prognostic for mortality and disease progression (death risk: HR = 3.3, 95% CI = 1.5-7.0, P = 0.02; progression risk: HR = 2.3, 95% CI = 1.2-4.8, P = 0.02), as well as positive lymph-node status (death risk: HR = 2.6, 95% CI = 1.1-6.3, P = 0.03; progression risk: HR = 2.2, 95% CI = 1.0-4.8, P = 0.04).

Conclusions: miR-21, miR-155 and miR-101 showed significant differences in invasive versus non-invasive IPMNs. miR-21 emerged as an independent prognostic biomarker in invasive IPMNs and should be validated in prospective studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / metabolism*
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / secondary
  • Adenocarcinoma, Papillary / metabolism*
  • Adenocarcinoma, Papillary / mortality
  • Adenocarcinoma, Papillary / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / secondary
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Proportional Hazards Models

Substances

  • MIRN101 microRNA, human
  • MIRN155 microRNA, human
  • MIRN21 microRNA, human
  • MicroRNAs