Abstract
Cancer initiation and progression are governed by both genetic and epigenetic events. Epigenetic alterations which include changes in DNA methylation, histone modifications, and noncoding RNA-mediated gene silencing are reversible and heritable. Aberrant epigenetic modifications are believed to be essential players in cancer initiation and progression. Recent advances in epigenetics have offered not only a deeper understanding of the underlying mechanisms of carcinogenesis but also new avenues for identification of clinically relevant putative biomarkers for the early detection, prognosis, monitoring of treatment response, and risk stratification of cancer patients. Following identification of cell-free nucleic acids in systematic circulation, cumulating evidences have demonstrated the potential of cell-free epigenetic biomarkers in the body fluids for cancer. Recently, the emergence of microRNAs as biomarkers has added an extra dimension to the “molecular signatures” of breast cancer. In this chapter, we summarize the currently published state-of-the-art research on the role of the circulating microRNAs in clinical utility for breast cancer, the most common cancer in women. In addition, we also discuss the current obstacles that have limited the routine use of epigenetic biomarkers and provide future perspectives, so that these novel cancer biomarkers can be readily developed for significant clinical improvement in the management of breast cancer patients.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abba M, Mudduluru G, Allgayer H (2012) MicroRNAs in cancer: small molecules, big chances. Anti-Cancer Agent Med Chem 12:733–743
Ai J, Zhang R, Li Y et al (2010) Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 391:73–77
Asaga S, Kuo C, Nguyen T et al (2011) Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem 57:84–91
Bala S, Tilahun Y, Taha O et al (2012) Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection. J Transl Med 10:151
Brase JC, Johannes M, Schlomm T et al (2011) Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 128:608–616
Budhu A, Ji J, Wang XW (2010) The clinical potential of microRNAs. J Hematol Oncol 3:37
Chan M, Liaw CS, Ji SM et al (2013) Identification of circulating microRNA signatures for breast cancer detection. Clin Cancer Res 19:4477–4487
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 34:455–462
Chen D, Goswami CP, Burnett RM et al (2014) Cancer affects microRNA expression, release, and function in cardiac and skeletal muscle. Cancer Res 74:4270–4281
Coates AS, Colleoni M, Goldhirsch A (2012) Is adjuvant chemotherapy useful for women with luminal a breast cancer? J Clin Oncol 30:1260–1263
Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51
Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791
Cuk K, Zucknick M, Heil J et al (2013) Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer 132:1602–1612
Davies C, Godwin J, Gray R et al (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784
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 59:1489–1496
Freres P, Josse C, Bovy N et al (2015) Neoadjuvant chemotherapy in breast cancer patients induces miR-34a and miR-122 expression. J Cell Physiol 230:473–481
Friel AM, Corcoran C, Crown J et al (2010) Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer. Breast Cancer Res Treat 123:613–625
Gezer U, Keskin S, Igci A et al (2014) Abundant circulating microRNAs in breast cancer patients fluctuate considerably during neoadjuvant chemotherapy. Oncol Lett 8:845–848
Gibbings DJ, Ciaudo C, Erhardt M et al (2009) Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol 11:1143–1149
Gidlof O, van der Brug M, Ohman J et al (2013) Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood 121(3908–3917):S3901–S3926
Gilad S, Meiri E, Yogev Y et al (2008) Serum microRNAs are promising novel biomarkers. PLoS One 3, e3148
Guo L-J, Zhang Q-Y (2012) Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med 30:680–686
Hasselmann DO, Rappl G, Tilgen W et al (2001) Extracellular tyrosinase mRNA within apoptotic bodies is protected from degradation in human serum. Clin Chem 47:1488–1489
Heneghan HM, Miller N, Lowery AJ et al (2010) Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 251:499–505
Heneghan HM, Miller N, Kerin MJ (2011) Circulating microRNAs: promising breast cancer biomarkers. Breast Cancer Res 13:402
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 33:828–834
Huang Z, Huang D, Ni S et al (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127:118–126
Iorio MV, Ferracin M, Liu CG et al (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070
Joosse SA, Muller V, Steinbach B et al (2014) Circulating cell-free cancer-testis MAGE-A RNA, BORIS RNA, let-7b and miR-202 in the blood of patients with breast cancer and benign breast diseases. Br J Cancer 111:909–917
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 118:2603–2614
Kodahl AR, Lyng MB, Binder H et al (2014a) Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer: a case control study. Mol Oncol 8:874–883
Kodahl AR, Zeuthen P, Binder H et al (2014b) Alterations in circulating miRNA levels following early-stage estrogen receptor-positive breast cancer resection in post-menopausal women. PLoS One 9:e101950
Kosaka N, Iguchi H, Ochiya T (2010a) Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101:2087–2092
Kosaka N, Iguchi H, Yoshioka Y et al (2010b) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285:17442–17452
Krichevsky AM, King KS, Donahue CP et al (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281
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 50:210–214
Lawrie CH, Gal S, Dunlop HM et al (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141:672–675
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854
Li Q, Liu M, Ma F et al (2014) Circulating miR-19a and miR-205 in serum may predict the sensitivity of luminal: a subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel. PLoS One 9:e104870
Liu L, Wang S, Cao X et al (2014) Analysis of circulating microRNA biomarkers for breast cancer detection: a meta-analysis. Tumour Biol 35:12245–12253
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408
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 18:5972–5982
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 34:163–169
Meng F, Henson R, Lang M et al (2006) Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 130:2113–2129
Meng F, Henson R, Wehbe-Janek H et al (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658
Muller V, Gade S, Steinbach B et al (2014) Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial. Breast Cancer Res Treat 147:61–68
Ng EK, Li R, Shin VY et al (2013) Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One 8:e53141
Park IH, Kang JH, Lee KS et al (2014) Identification and clinical implications of circulating microRNAs for estrogen receptor-positive breast cancer. Tumour Biol 35:12173–12180
Qian B, Katsaros D, Lu L et al (2009) High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1. Breast Cancer Res Treat 117:131–140
Qu KZ, Zhang K, Li H et al (2011) Circulating microRNAs as biomarkers for hepatocellular carcinoma. J Clin Gastroenterol 45:355–360
Rechavi O, Erlich Y, Amram H et al (2009) Cell contact-dependent acquisition of cellular and viral nonautonomously encoded small RNAs. Genes Dev 23:1971–1979
Reid G, Kirschner MB, van Zandwijk N (2011) Circulating microRNAs: association with disease and potential use as biomarkers. Crit Rev Oncol Hematol 80:193–208
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:R90
Sakr BJ, Dizon DS (2011) Breast cancer: adjuvant modalities. Clin Obstet Gynecol 54:150–156
Sato F, Tsuchiya S, Terasawa K et al (2009) Intra-platform repeatability and inter-platform comparability of microRNA microarray technology. PLoS One 4, e5540
Shen J, Hu Q, Schrauder M et al (2014) Circulating miR-148b and miR-133a as biomarkers for breast cancer detection. Oncotarget 5:5284–5294
Siegel R, Ma J, Zou Z et al (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29
Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283
Sochor M, Basova P, Pesta M et al (2014) Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum. BMC Cancer 14:448
Taback B, Giuliano AE, Hansen NM et al (2003) Detection of tumor-specific genetic alterations in bone marrow from early-stage breast cancer patients. Cancer Res 63:1884–1887
Tsang JC, Lo YM (2007) Circulating nucleic acids in plasma/serum. Pathology 39:197–207
Turchinovich A, Weiz L, Langheinz A et al (2011) Characterization of extracellular circulating microRNA. Nucleic Acids Res 39:7223–7233
Vickers KC, Palmisano BT, Shoucri BM et al (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423–433
Wang K, Zhang S, Weber J et al (2010) Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res 38:7248–7259
Wang H, Tan G, Dong L et al (2012) Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One 7:e34210
Weickmann JL, Glitz DG (1982) Human ribonucleases: quantitation of pancreatic-like enzymes in serum, urine, and organ preparations. J Biol Chem 257:8705–8710
Wu Q, Lu Z, Li H et al (2011) Next-generation sequencing of microRNAs for breast cancer detection. J Biomed Biotechnol 2011:597145
Wu X, 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
Yan LX, Huang XF, Shao Q et al (2008) MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14:2348–2360
Yang Y, Qian J, Chen Y et al (2014) Prognostic role of circulating microRNA-21 in cancers: evidence from a meta-analysis. Tumour Biol 35:6365–6371
Yu DC, Li QG, Ding XW et al (2011) Circulating microRNAs: potential biomarkers for cancer. Int J Mol Sci 12:2055–2063
Zearo S, Kim E, Zhu Y et al (2014) MicroRNA-484 is more highly expressed in serum of early breast cancer patients compared to healthy volunteers. BMC Cancer 14:200
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 30:477
Zhang C, Wang C, Chen X et al (2010) Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma. Clin Chem 56:1871–1879
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:e13735
Zhao R, Wu J, Jia W et al (2011) Plasma miR-221 as a predictive biomarker for chemoresistance in breast cancer patients who previously received neoadjuvant chemotherapy. Onkologie 34:675–680
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Yang, YL. (2016). Thinking Small: Circulating microRNAs as Novel Biomarkers for Diagnosis, Prognosis, and Treatment Monitoring in Breast Cancer. In: Jurga, S., Erdmann (Deceased), V., Barciszewski, J. (eds) Modified Nucleic Acids in Biology and Medicine. RNA Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-34175-0_10
Download citation
DOI: https://doi.org/10.1007/978-3-319-34175-0_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-34173-6
Online ISBN: 978-3-319-34175-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)