Medical College of Wisconsin
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Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls. Carcinogenesis 2012 Apr;33(4):828-34

Date

02/03/2012

Pubmed ID

22298638

DOI

10.1093/carcin/bgs030

Scopus ID

2-s2.0-84859604906 (requires institutional sign-in at Scopus site)   187 Citations

Abstract

It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma/serum, which can be detected and are potentially disease specific. However, the lack of suitable endogenous controls for serum miRNA detection is the restriction for the widely usage of this kind of biomarkers and for the between-laboratory comparison of the findings. We first systematically screened for endogenous control miRNAs (ECMs) by testing 10 pooling samples (using both Solexa sequencing and TaqMan low density array) and 50 individual samples (using quantitative reverse transcription-PCR) of different cancer traits and healthy controls. Then we assessed serum miRNAs used as potential biomarkers for breast cancer risk prediction based on a two-stage case-control analysis, including 48 breast cancer patients and 48 controls for the discovery stage and 76 breast cancer patients and 76 controls for validation. We identified two candidate ECMs (miRNA-191 and miRNA-484). Normalized by the two ECMs, we found four miRNAs (miR-16, miR-25, miR-222 and miR-324-3p) that were consistently differentially expressed between breast cancer cases and controls. The area under the receiver operating characteristic curve is 0.954 for the four-miRNA signature in the discovery stage (sensitivity = 0.917 and specificity = 0.896) and 0.928 in the validation stage (sensitivity = 0.921 and specificity = 0.934). In conclusion, the four-miRNA signature from serum may serve as a non-invasive prediction biomarker for breast cancer. Furthermore, we proposed the combination of miRNA-484 and miRNA-191 as endogenous control for serum miRNA detection, at least for most common cancers.

Author List

Hu Z, Dong J, Wang LE, Ma H, Liu J, Zhao Y, Tang J, Chen X, Dai J, Wei Q, Zhang C, Shen H

Author

Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Breast Neoplasms
Case-Control Studies
Female
Genetic Predisposition to Disease
Humans
MicroRNAs
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction