High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.

<h4>Background</h4>Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throug...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Elisa Giovannetti, Arjan van der Velde, Niccola Funel, Enrico Vasile, Vittorio Perrone, Leticia G Leon, Nelide De Lio, Amir Avan, Sara Caponi, Luca E Pollina, Valentina Gallá, Hiroko Sudo, Alfredo Falcone, Daniela Campani, Ugo Boggi, Godefridus J Peters
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
Materias:
R
Q
Acceso en línea:https://doaj.org/article/78d81e5485f2461cb502a7b869c679ef
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:78d81e5485f2461cb502a7b869c679ef
record_format dspace
spelling oai:doaj.org-article:78d81e5485f2461cb502a7b869c679ef2021-11-18T08:08:49ZHigh-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.1932-620310.1371/journal.pone.0049145https://doaj.org/article/78d81e5485f2461cb502a7b869c679ef2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23155457/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities 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.<h4>Methodology/principal findings</h4>High-resolution miRNA profiles were obtained with the Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28 days), carefully selected according to their outcome (OS<12 (N = 13) vs. OS>30 months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed 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 discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser-microdissected PDACs from 60 resected patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according 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 independent factor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all the factors influencing outcome.<h4>Conclusions/significance</h4>Through comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC.Elisa GiovannettiArjan van der VeldeNiccola FunelEnrico VasileVittorio PerroneLeticia G LeonNelide De LioAmir AvanSara CaponiLuca E PollinaValentina GalláHiroko SudoAlfredo FalconeDaniela CampaniUgo BoggiGodefridus J PetersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49145 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elisa Giovannetti
Arjan van der Velde
Niccola Funel
Enrico Vasile
Vittorio Perrone
Leticia G Leon
Nelide De Lio
Amir Avan
Sara Caponi
Luca E Pollina
Valentina Gallá
Hiroko Sudo
Alfredo Falcone
Daniela Campani
Ugo Boggi
Godefridus J Peters
High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.
description <h4>Background</h4>Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities 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.<h4>Methodology/principal findings</h4>High-resolution miRNA profiles were obtained with the Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28 days), carefully selected according to their outcome (OS<12 (N = 13) vs. OS>30 months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed 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 discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser-microdissected PDACs from 60 resected patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according 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 independent factor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all the factors influencing outcome.<h4>Conclusions/significance</h4>Through comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC.
format article
author Elisa Giovannetti
Arjan van der Velde
Niccola Funel
Enrico Vasile
Vittorio Perrone
Leticia G Leon
Nelide De Lio
Amir Avan
Sara Caponi
Luca E Pollina
Valentina Gallá
Hiroko Sudo
Alfredo Falcone
Daniela Campani
Ugo Boggi
Godefridus J Peters
author_facet Elisa Giovannetti
Arjan van der Velde
Niccola Funel
Enrico Vasile
Vittorio Perrone
Leticia G Leon
Nelide De Lio
Amir Avan
Sara Caponi
Luca E Pollina
Valentina Gallá
Hiroko Sudo
Alfredo Falcone
Daniela Campani
Ugo Boggi
Godefridus J Peters
author_sort Elisa Giovannetti
title High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.
title_short High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.
title_full High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.
title_fullStr High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.
title_full_unstemmed High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.
title_sort high-throughput microrna (mirnas) arrays unravel the prognostic role of mir-211 in pancreatic cancer.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/78d81e5485f2461cb502a7b869c679ef
work_keys_str_mv AT elisagiovannetti highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT arjanvandervelde highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT niccolafunel highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT enricovasile highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT vittorioperrone highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT leticiagleon highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT nelidedelio highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT amiravan highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT saracaponi highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT lucaepollina highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT valentinagalla highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT hirokosudo highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT alfredofalcone highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT danielacampani highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT ugoboggi highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
AT godefridusjpeters highthroughputmicrornamirnasarraysunraveltheprognosticroleofmir211inpancreaticcancer
_version_ 1718422175805865984