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

S. Caponi, N. Funel, A. E. Frampton, F. Mosca, L. Santarpia, A. G. Van der Velde, L. R. Jiao, N. De Lio, A. Falcone, G. Kazemier, G. A. Meijer, H. M. Verheul, E. Vasile, G. J. Peters, U. Boggi, E. Giovannetti

Research output: Contribution to journalArticle

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 withoverall (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 diseaseprogression (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.

Original languageEnglish
Article numbermds513
Pages (from-to)734-741
Number of pages8
JournalAnnals of Oncology
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2013

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Keywords

  • MicroRNA-101
  • MicroRNA-155
  • MicroRNA-21
  • Outcome
  • Pancreatic intraductal papillary mucinous neoplasms

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Caponi, S., Funel, N., Frampton, A. E., Mosca, F., Santarpia, L., Van der Velde, A. G., Jiao, L. R., De Lio, N., Falcone, A., Kazemier, G., Meijer, G. A., Verheul, H. M., Vasile, E., Peters, G. J., Boggi, U., & Giovannetti, E. (2013). The good, the bad and the ugly: A tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms. Annals of Oncology, 24(3), 734-741. [mds513]. https://doi.org/10.1093/annonc/mds513