Circulating Micro-RNAs as Potential Blood-Based Markers for Early Stage Breast Cancer Detection

Department of Obstetrics and Gynaecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
PLoS ONE (Impact Factor: 3.23). 01/2012; 7(1):e29770. DOI: 10.1371/journal.pone.0029770
Source: PubMed


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.
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).
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.
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.

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Available from: Michael G Schrauder, Oct 07, 2015
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    • "Among the identified cancers, higher mortality rates have been reported for breast, ovarian, gastric, prostate and testicular-germ cell cancers in individuals of recent African ancestry compared to individuals of either European or Asian descent (p < 0.001) [51-54]. Of particular interest is hsa-mir-202 which contained one of the most highly population-differentiated variants in our dataset and is one of two miRNAs currently under investigation as a circulating blood-based marker for the detection of non-Hodgkin lymphoma and early stage breast cancer [42,55]. Recent in vitro functional data demonstrated that the T-allele was protective against breast cancer mortality by first increasing mature hsa-mir-202 expression levels, leading to subsequent down-regulation of its gene targets, including cancer related genes CRYBB2, DICER1, SART1, S100A8, P2RX3, and BRCA1[42]. "
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    ABSTRACT: Background: MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes.
    BMC Medical Genomics 08/2014; 7(1):53. DOI:10.1186/1755-8794-7-53 · 2.87 Impact Factor
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    • "To date , only one study has evaluated the levels of circulating miR - 202 in the blood of breast cancer patients . This study showed that miR - 202 was significantly upregulated in whole blood samples of early - stage breast cancer patients performing microarray and quantitative PCR ( Schrauder et al , 2012 ) . "
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    • "Over 200 miRNAs were detected, and we detected a change in the expression of a handful of these miRNAs following subsequent stimulation with FCS and treatment with dexamethasone. All of these miRNAs have previously been shown to be associated with cancer, for example, miR-371-5p is associated with gastric cancer [27], miR-718 with breast cancer [28], miR-1181 with ovarian cancer [29], miR-1207-5p is associated with a novel cancer treatment, isoliquiritigenin [30], miR-1915 is associated with drug resistance in colorectal cancer [31] and miR-3663-3p is associated with skin cancer [32]. Although these miRNAs have a role in aberrant cellular proliferation, this is the first time that these miRNAs have reported to be expressed in proliferating primary ASM cells. "
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