A ranking-based meta-analysis reveals let-7 family as a meta-signature for grade classification in breast cancer

Date
2015
Authors
Oztemur, Y.
Bekmez, T.
Aydos, A.
Yulug I.G.
Bozkurt, B.
Dedeoglu, B.G.
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Supervisor
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Source Title
PLoS ONE
Print ISSN
19326203
Electronic ISSN
Publisher
Public Library of Science
Volume
10
Issue
5
Pages
Language
English
Type
Article
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Abstract

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.

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Keywords
B lymphocyte induced maturation protein 1, biological marker, dendritic cell lysosome associated membrane protein, heme oxygenase 1, mammalian target of rapamycin, messenger RNA, microRNA, microRNA 30a 3p, microRNA 30a 5p, microRNA 320, microRNA 7, microRNA 99a, 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, unclassified drug, vasculotropin, apoptosis, Article, breast cancer, cancer grading, cell cycle, down regulation, gene, gene expression regulation, genetic association, HMOX1 gene, human, human tissue, IQGAP3 gene, LAMP3 gene, LMNB2 gene, MCM2 gene, ME1 gene, POLA2 gene, POLR2C gene, PRDM1 gene, PSAT1 gene, RDH10 gene, reverse transcription polymerase chain reaction, SAMSN1 gene, SEC24A gene, SELL gene, signal transduction, SLC16A3 gene, SLC25A13 gene, SLC7A5 gene, SOAT1 gene, SOCS1 gene, SQSTM1 gene, SRM gene, STMN1 gene, TCF19 gene, TRIP13 gene, TXNRD1 gene, TYMS gene, upregulation
Citation
Published Version (Please cite this version)