Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.

<h4>Introduction</h4>MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable...

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Autores principales: Michael G Schrauder, Reiner Strick, Rüdiger Schulz-Wendtland, Pamela L Strissel, Laura Kahmann, Christian R Loehberg, Michael P Lux, Sebastian M Jud, Arndt Hartmann, Alexander Hein, Christian M Bayer, Mayada R Bani, Swetlana Richter, Boris R Adamietz, Evelyn Wenkel, Claudia Rauh, Matthias W Beckmann, Peter A Fasching
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:7ffd56597d53499ebe1fe670980c79362021-11-18T07:30:51ZCirculating micro-RNAs as potential blood-based markers for early stage breast cancer detection.1932-620310.1371/journal.pone.0029770https://doaj.org/article/7ffd56597d53499ebe1fe670980c79362012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22242178/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls.<h4>Methods</h4>We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718).<h4>Results</h4>Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202.<h4>Conclusions</h4>MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use.Michael G SchrauderReiner StrickRüdiger Schulz-WendtlandPamela L StrisselLaura KahmannChristian R LoehbergMichael P LuxSebastian M JudArndt HartmannAlexander HeinChristian M BayerMayada R BaniSwetlana RichterBoris R AdamietzEvelyn WenkelClaudia RauhMatthias W BeckmannPeter A FaschingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29770 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Michael G Schrauder
Reiner Strick
Rüdiger Schulz-Wendtland
Pamela L Strissel
Laura Kahmann
Christian R Loehberg
Michael P Lux
Sebastian M Jud
Arndt Hartmann
Alexander Hein
Christian M Bayer
Mayada R Bani
Swetlana Richter
Boris R Adamietz
Evelyn Wenkel
Claudia Rauh
Matthias W Beckmann
Peter A Fasching
Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.
description <h4>Introduction</h4>MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls.<h4>Methods</h4>We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718).<h4>Results</h4>Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202.<h4>Conclusions</h4>MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use.
format article
author Michael G Schrauder
Reiner Strick
Rüdiger Schulz-Wendtland
Pamela L Strissel
Laura Kahmann
Christian R Loehberg
Michael P Lux
Sebastian M Jud
Arndt Hartmann
Alexander Hein
Christian M Bayer
Mayada R Bani
Swetlana Richter
Boris R Adamietz
Evelyn Wenkel
Claudia Rauh
Matthias W Beckmann
Peter A Fasching
author_facet Michael G Schrauder
Reiner Strick
Rüdiger Schulz-Wendtland
Pamela L Strissel
Laura Kahmann
Christian R Loehberg
Michael P Lux
Sebastian M Jud
Arndt Hartmann
Alexander Hein
Christian M Bayer
Mayada R Bani
Swetlana Richter
Boris R Adamietz
Evelyn Wenkel
Claudia Rauh
Matthias W Beckmann
Peter A Fasching
author_sort Michael G Schrauder
title Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.
title_short Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.
title_full Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.
title_fullStr Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.
title_full_unstemmed Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.
title_sort circulating micro-rnas as potential blood-based markers for early stage breast cancer detection.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/7ffd56597d53499ebe1fe670980c7936
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