A ranking-based meta-analysis reveals let-7 family as a meta-signature for grade classification in breast cancer
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Breast cancer is one of the most important causes of cancer-related deaths worldwide in women. In addition to gene expression studies, the progressing work in the miRNA area including miRNA microarray studies, brings new aspects to the research on the cancer development and progression. Microarray technology has been widely used to find new biomarkers in research and many transcriptomic microarray studies are available in public databases. In this study, the breast cancer miRNA and mRNA microarray studies were collected according to the availability of their data and clinical information, and combined by a newly developed ranking-based meta-analysis approach to find out candidate miRNA biomarkers (meta-miRNAs) that classify breast cancers according to their grades and explain the relation between miRNAs and mRNAs. This approach provided meta-miRNAs specific to breast cancer grades, pointing out let-7 family members as grade classifiers. The qRTPCR studies performed with independent breast tumors confirmed the potential biomarker role of let-7 family members (meta-miRNAs). The concordance between the meta-mRNAs and miRNA target genes specific to tumor grade (common genes) supported the idea of mRNAs as miRNA targets. The pathway analysis results showed that most of the let-7 family miRNA targets, and also common genes, were significantly taking part in cancer-related pathways. The qRT-PCR studies, together with bioinformatic analyses, confirmed the results of meta-analysis approach, which is dynamic and allows combining datasets from different platforms. © 2015 Oztemur et al.
KeywordsB lymphocyte induced maturation protein 1
dendritic cell lysosome associated membrane protein
heme oxygenase 1
mammalian target of rapamycin
microRNA 30a 3p
microRNA 30a 5p
microRNA let 7
microRNA let 7a
microRNA let 7b
microRNA let 7c
microRNA let 7d
microRNA let 7e
microRNA let 7f
microRNA let 7g
microRNA let 7i
minichromosome maintenance protein 2
mitogen activated protein kinase
monocarboxylate transporter 4
suppressor of cytokine signaling 1
thioredoxin reductase 1
transforming growth factor beta
gene expression regulation
reverse transcription polymerase chain reaction
Published Version (Please cite this version)http://dx.doi.org/10.1371/journal.pone.0126837
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