TY - JOUR
T1 - The good, the bad and the ugly
T2 - A tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms
AU - Caponi, S.
AU - Funel, N.
AU - Frampton, A. E.
AU - Mosca, F.
AU - Santarpia, L.
AU - Van der Velde, A. G.
AU - Jiao, L. R.
AU - De Lio, N.
AU - Falcone, A.
AU - Kazemier, G.
AU - Meijer, G. A.
AU - Verheul, H. M.
AU - Vasile, E.
AU - Peters, G. J.
AU - Boggi, U.
AU - Giovannetti, E.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
KW - MicroRNA-101
KW - MicroRNA-155
KW - MicroRNA-21
KW - Outcome
KW - Pancreatic intraductal papillary mucinous neoplasms
UR - http://www.scopus.com/inward/record.url?scp=84874562085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874562085&partnerID=8YFLogxK
U2 - 10.1093/annonc/mds513
DO - 10.1093/annonc/mds513
M3 - Article
C2 - 23139258
AN - SCOPUS:84874562085
VL - 24
SP - 734
EP - 741
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 3
M1 - mds513
ER -