Abstract
It is believed that microRNAs have potential as circulating biomarkers of disease; however, successful clinical implementation remains a challenge. This chapter highlights broad variations in approaches to microRNA analysis where whole blood, serum and plasma have each been employed as viable sources. Further discrepancies in approaches are seen in endogenous controls and extraction methods utilized. This has resulted in contradictory publications, even when the same microRNA is targeted in the same disease setting.
Analysis of blood samples highlighted the impact of both collection method and storage, on the microRNA profile. Analysis of a panel of microRNAs across whole blood, serum, and plasma originating from the same individual emphasized the impact of starting material on microRNA profile. This is a highly topical field of research with immense potential for translation into the clinical setting. Standardization of sample harvesting, processing and analysis will be key to this translation. Methods of sample harvesting, preservation, and analysis are outlined, with important mitigating factors highlighted.
Key words
- Circulating microRNAs
- Breast Cancer
- Whole blood
- Serum
- Plasma
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Chen X, Liang H, Zhang J et al (2012) Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol 22(3):125–132. doi:10.1016/j.tcb.2011.12.001, doi:S0962-8924(11)00238-8 [pii]
Mar-Aguilar F, Mendoza-Ramirez JA, Malagon-Santiago I et al (2013) Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers 34(3):163–169. doi:10.3233/Dma-120957
Heneghan HM, Miller N, Kelly R et al (2010) Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist 15(7):673–682. doi:10.1634/theoncologist.2010-0103, doi:theoncologist.2010-0103 [pii]
Wang F, Zheng Z, Guo J et al (2010) Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol 119(3):586–593. doi:10.1016/j.ygyno.2010.07.021, S0090-8258(10)00550-0 [pii]
Cookson VJ, Bentley MA, Hogan BV et al (2012) Circulating microRNA profiles reflect the presence of breast tumours but not the profiles of microRNAs within the tumours. Cell Oncol (Dordr) 35(4):301–308. doi:10.1007/s13402-012-0089-1
Ng EKO, Li RFN, Shin VY et al (2013) Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One 8(1), e53141, doi:ARTN e53141. DOI 10.1371/journal.pone.0053141
Wu XW, Somlo G, Yu Y et al (2012) De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. J Transl Med 10:42. doi:10.1186/1479-5876-10-42
Schwarzenbach H, Milde-Langosch K, Steinbach B et al (2012) Diagnostic potential of PTEN-targeting miR-214 in the blood of breast cancer patients. Breast Cancer Res Treat 134(3):933–941. doi:10.1007/s10549-012-1988-6
Schrauder MG, Strick R, Schulz-Wendtland R et al (2012) Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection. PLoS One 7(1), e29770. doi:10.1371/journal.pone.0029770, PONE-D-11-17907 [pii]
Shaffer J (2012) miRNA profiling from blood — challenges and recommendations. Qiagen
Kirschner MB, Kao SC, Edelman JJ et al (2011) Haemolysis during sample preparation alters microRNA content of plasma. PLoS One 6(9), e24145. doi:10.1371/journal.pone.0024145
Sethi P, Lukiw WJ (2009) Micro-RNA abundance and stability in human brain: specific alterations in Alzheimer’s disease temporal lobe neocortex. Neurosci Lett 459(2):100–104. doi:10.1016/j.neulet.2009.04.052
Kroh EM, Parkin RK, Mitchell PS et al (2010) Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 50(4):298–301. doi:10.1016/j.ymeth.2010.01.032
Mitchell PS, Parkin RK, Kroh EM et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105(30):10513–10518. doi:10.1073/pnas.0804549105, 0804549105 [pii]
Leidner RS, Li L, Thompson CL (2013) Dampening enthusiasm for circulating MicroRNA in breast cancer. PLoS One 8(3), e57841. doi:10.1371/journal.pone.0057841
McDonald JS, Milosevic D, Reddi HV et al (2011) Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem 57(6):833–840. doi:10.1373/clinchem.2010.157198
Heneghan HM, Miller N, Lowery AJ et al (2010) Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 251(3):499–505. doi:10.1097/Sla.0b013e3181cc939f
Si HY, Sun XM, Chen YJ et al (2013) Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin 139(2):223–229. doi:10.1007/s00432-012-1315-y
Zeng RC, Zhang W, Yan XQ et al (2013) Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer. Med Oncol 30(1):477. doi:10.1007/S12032-013-0477-Z
McDermott AM, Kerin MJ, Miller N (2013) Identification and validation of miRNAs as endogenous controls for RQ-PCR in blood specimens for breast cancer studies. PLoS One 8(12), e83718. doi:10.1371/journal.pone.0083718
Anfossi S, Giordano A, Gao H et al (2014) High serum miR-19a levels Are associated with inflammatory breast cancer and Are predictive of favorable clinical outcome in patients with metastatic HER2(+) inflammatory breast cancer. PLoS One 9(1), e83113. doi:10.1371/journal.pone.0083113
Wang HJ, Tan G, Dong L et al (2012) Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One 7(4), e34210. doi:10.1371/journal.pone.0034210
Chen W, Cai F, Zhang B et al (2013) The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol 34(1):455–462. doi:10.1007/s13277-012-0570-5
Kumar S, Keerthana R, Pazhanimuthu A et al (2013) Overexpression of circulating miRNA-21 and miRNA-146a in plasma samples of breast cancer patients. Indian J Biochem Biophys 50(3):210–214
Pritchard CC, Kroh E, Wood B et al (2012) Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res (Phila) 5(3):492–497. doi:10.1158/1940-6207.CAPR-11-0370
Sieuwerts AM, Mostert B, Bolt-de Vries J et al (2011) mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin Cancer Res 17(11):3600–3618. doi:10.1158/1078-0432.CCR-11-0255
Khan S, Brougham CL, Ryan J et al (2013) miR-379 regulates cyclin B1 expression and is decreased in breast cancer. PLoS One 8(7):e68753. doi:10.1371/journal.pone.0068753
Waters PS, Dwyer RM, Brougham C et al (2014) Impact of tumour epithelial subtype on circulating microRNAs in breast cancer patients. PLoS One 9(3), e90605. doi:10.1371/journal.pone.0090605
Waters PS, McDermott AM, Wall D et al (2012) Relationship between circulating and tissue microRNAs in a murine model of breast cancer. PLoS One 7(11), e50459. doi:10.1371/journal.pone.0050459
Wang PY, Gong HT, Li BF et al (2013) Higher expression of circulating miR-182 as a novel biomarker for breast cancer. Oncol Lett 6(6):1681–1686. doi:10.3892/Ol.2013.1593
Eichelser C, Flesch-Janys D, Chang-Claude J et al (2013) Deregulated serum concentrations of circulating cell-free MicroRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression. Clin Chem 59(10):1489–1496. doi:10.1373/clinchem.2013.205161
Sun Y, Wang MJ, Lin GG et al (2012) Serum MicroRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One 7(10), e47003. doi:10.1371/journal.pone.0047003
van Schooneveld E, Wouters MCA, Van der Auwera I et al (2012) Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers. Breast Cancer Res 14(1):R34. doi:10.1186/Bcr3127
Asaga S, Kuo C, Nguyen T et al (2011) Direct serum assay for MicroRNA-21 concentrations in early and advanced breast cancer. Clin Chem 57(1):84–91. doi:10.1373/clinchem.2010.151845
Zhu W, Qin W, Atasoy U et al (2009) Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes 2:89. doi:10.1186/1756-0500-2-89
Li J, Zhang Y, Zhang W et al (2013) Genetic heterogeneity of breast cancer metastasis may be related to miR-21 regulation of TIMP-3 in translation. Int J Surg Oncol 2013:875078. doi:10.1155/2013/875078
Godfrey AC, Xu Z, Weinberg CR et al (2013) Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort. Breast Cancer Res 15(3):R42. doi:10.1186/bcr3428
Tang D, Zhang Q, Zhao S et al (2013) The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer. Clin Biochem 46(10-11):926–932. doi:10.1016/j.clinbiochem.2013.01.027
Zhao FL, Hu GD, Wang XF et al (2012) Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer. J Int Med Res 40(3):859–866
Guo LJ, Zhang QY (2012) Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med 30(3):680–686. doi:10.3892/ijmm.2012.1021
Wang X, Wu X, Yan L et al (2012) Serum miR-103 as a potential diagnostic biomarker for breast cancer. Nan Fang Yi Ke Da Xue Xue Bao 32(5):631–634
Wu Q, Wang C, Lu Z et al (2012) Analysis of serum genome-wide microRNAs for breast cancer detection. Clin Chim Acta 413(13-14):1058–1065. doi:10.1016/j.cca.2012.02.016
Hu Z, Dong J, Wang LE et al (2012) Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls. Carcinogenesis 33(4):828–834. doi:10.1093/carcin/bgs030, doi:bgs030 [pii]
Appaiah HN, Goswami CP, Mina LA et al (2011) Persistent upregulation of U6:SNORD44 small RNA ratio in the serum of breast cancer patients. Breast Cancer Res 13(5):R86. doi:10.1186/bcr2943
Wu Q, Lu Z, Li H et al (2011) Next-generation sequencing of microRNAs for breast cancer detection. J Biomed Biotechnol 2011:597145. doi:10.1155/2011/597145
Gotte M (2010) MicroRNAs in breast cancer pathogenesis. Minerva Ginecol 62(6):559–571
Roth C, Rack B, Muller V et al (2010) Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res 12(6):R90. doi:10.1186/bcr2766, doi:bcr2766 [pii]
Guo L, Zhao Y, Yang S et al (2013) Genome-wide screen for aberrantly expressed miRNAs reveals miRNA profile signature in breast cancer. Mol Biol Rep 40(3):2175–2186. doi:10.1007/s11033-012-2277-5
Jung EJ, Santarpia L, Kim J et al (2012) Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer 118(10):2603–2614. doi:10.1002/cncr.26565
Cuk K, Zucknick M, Madhavan D et al (2013) Plasma microRNA panel for minimally invasive detection of breast cancer. PLoS One 8(10), e76729. doi:10.1371/journal.pone.0076729
Liu JJ, Mao QX, Liu Y et al (2013) Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients. Chin J Cancer Res 25(1):46–54. doi:10.3978/j.issn.1000-9604.2012.11.04
Madhavan D, Zucknick M, Wallwiener M et al (2012) Circulating miRNAs as Surrogate Markers for Circulating Tumor Cells and Prognostic Markers in Metastatic Breast Cancer. Clin Cancer Res 18(21):5972–5982. doi:10.1158/1078-0432.Ccr-12-1407
Zhao RH, Wu JN, Jia WJ et al (2011) Plasma miR-221 as a Predictive Biomarker for Chemoresistance in Breast Cancer Patients who Previously Received Neoadjuvant Chemotherapy. Onkologie 34(12):675–680. doi:10.1159/000334552
Zhao H, Shen J, Medico L et al (2010) A Pilot Study of Circulating miRNAs as Potential Biomarkers of Early Stage Breast Cancer. PLoS One 5(10), e13735. doi:10.1371/journal.pone.0013735
Tjensvoll K, Svendsen KN, Reuben JM et al (2012) miRNA expression profiling for identification of potential breast cancer biomarkers. Biomarkers 17(5):463–470. doi:10.3109/1354750X.2012.686061
Acknowledgements
This material is based upon works supported by the Irish Cancer Society collaborative cancer research centre BREAST-PREDICT Grant CCRC13GAL and funding agency “Breast Cancer Research”.
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O’Brien, K.P. et al. (2017). Circulating MicroRNAs in Cancer. In: Rani, S. (eds) MicroRNA Profiling. Methods in Molecular Biology, vol 1509. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6524-3_12
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DOI: https://doi.org/10.1007/978-1-4939-6524-3_12
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