Experiment Detail



Experiment IDEXP00202
ReferenceTitle: High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211in pancreatic cancer.
Author: Giovannetti E, van der Velde A, Funel N, Vasile E, Perrone V, Leon LG, De Lio N, Avan A, Caponi S, Pollina LE, Gallá V, Sudo H, Falcone A, Campani D, Boggi U, Peters GJ.
Journal: PLoS One. 2012;7(11):e49145. doi: 10.1371/journal.pone.0049145. Epub 2012 Nov 14.
Abstract: BACKGROUND: Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognosticfactors is warranted. Recently miRNAs emerged as diagnostic biomarkers andinnovative therapeutic targets, while high-throughput arrays are opening newopportunities to evaluate whether they can predict clinical outcome. The present study evaluated whether comprehensive miRNA expression profiling correlated with overall survival (OS) in resected PDAC patients.METHODOLOGY/PRINCIPAL FINDINGS: High-resolution miRNA profiles were obtained withthe Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA wassuccessfully isolated from paraffin-embedded primary tumors of 19 out of 26stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000mg/m(2)/day, days-1/8/15, every 28 days), carefully selected according to theiroutcome (OS<12 (N = 13) vs. OS>30 months (N = 6), i.e. short/long-OS). Highlystringent statistics included t-test, distance matrix with Spearman-rankedcorrelation, and iterative approaches. Unsupervised hierarchical analysisrevealed that PDACs clustered according to their short/long-OS classification,while the feature selection algorithm RELIEF identified the top 4 discriminating miRNAs between the two groups. These miRNAs target more than 1500 transcripts,including 169 targeted by two or more. MiR-211 emerged as the best discriminatingmiRNA, with significantly higher expression in long- vs. short-OS patients. Theexpression of this miRNA was subsequently assessed by quantitative-PCR in anindependent cohort of laser-microdissected PDACs from 60 resected patientstreated with the same gemcitabine regimen. Patients with low miR-211 expressionaccording to median value had a significantly shorter median OS (14.8,95%CI = 13.1-16.5, vs. 25.7 months, 95%CI = 16.2-35.1, log-rank-P = 0.004).Multivariate analysis demonstrated that low miR-211 expression was an independentfactor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all thefactors influencing outcome.CONCLUSIONS/SIGNIFICANCE: Through comprehensive microarray analysis and PCRvalidation we identified miR-211 as a prognostic factor in resected PDAC. Theseresults prompt further prospective studies and research on the biological role ofmiR-211 in PDAC.
PMID: 23155457
Expressiion ProfileDescription: High-throughput microRNA (miRNAs) arrays in pancreatic cancer
Organism: Homo sapiens
GEO ID: GSE38781
Platform: GPL14903
Number of samples: 19
Design and SampleCancer Type: pancreatic cancer
Cancer SubType: N/D
Cell Line: N/D
Experimental Design: poor outcome vs good outcome
Case Sample: short time survival
Control Sample: long time survival
Num of Case: 13
Num of Control: 6
Quantification Software: Limma
Num of miRNAs: 1211
IdentificationNum of Up: 29
Num of Down: 17