Abstract
Deregulation of microRNA expression has been shown to play an important role in human malignancies. The identification of circulating-free miRNAs in biofluids a decade ago led to great enthusiasm and motivation to develop non-invasive tests based on the expression of these small non-coding RNAs. Herein, we review the progress within the field of research for identifying circulating miRNA cancer biomarkers and discuss the advantages and challenges associated with this. We also discuss the methodological and analytical variables, which may influence the final miRNA quantification and the importance of standardizing pre-analytical, analytical, and post-analytical processes in order to enable a successful translation of the results from basic research into the clinics.
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Abbreviations
- EDTA:
-
Ethylenediaminetetraacetic acid
- HDL:
-
High-density lipoproteins
- LDCT:
-
Low-dose computed tomography
- MGCT:
-
Malignant germ cell tumors
- miRNA:
-
MicroRNA
- MSC:
-
miRNA signature classifier
- Nt:
-
Nucleotides
- qPCR:
-
Quantitative polymerase chain reaction
- snoRNA:
-
Small nucleolar RNA
- UTR:
-
Untranslated region
References
Afonso-Grunz F, Muller S (2015) Principles of miRNA-mRNA interactions: beyond sequence complementarity. Cell Mol Life Sci 72(16):3127–3141
Arroyo JD et al (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108(12):5003–5008
Ayers L et al (2011) Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay. Thromb Res 127(4):370–377
Benjamin H et al (2016) Analytical validity of a microRNA-based assay for diagnosing indeterminate thyroid FNA smears from routinely prepared cytology slides. Cancer Cytopathol 124(10):711–721
Berindan-Neagoe I et al (2014) MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA Cancer J Clin 64(5):311–336
Beutler E, Gelbart T, Kuhl W (1990) Interference of heparin with the polymerase chain reaction. Biotechniques 9(2):166
Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69(3):89–95
Blondal T et al (2013) Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods 59(1):S1–S6
Boeri M et al (2011) MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci U S A 108(9):3713–3718
Brennecke J et al (2005) Principles of microRNA-target recognition. PLoS Biol 3(3):e85
Brunet-Vega A et al (2015) Variability in microRNA recovery from plasma: comparison of five commercial kits. Anal Biochem 488:28–35
Bustin SA (2010) Why the need for qPCR publication guidelines? The case for MIQE. Methods 50(4):217–226
Bustin SA et al (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55(4):611–622
Bustin S et al (2015) Variability of the reverse transcription step: practical implications. Clin Chem 61(1):202–212
Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866
Chang TC et al (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26(5):745–752
Chen X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006
Cortez MA et al (2011) MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol 8(8):467–477
Egidi MG et al (2013) Circulating microRNAs and kallikreins before and after radical prostatectomy: are they really prostate cancer markers? Biomed Res Int 2013:241780
El-Hefnawy T et al (2004) Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics. Clin Chem 50(3):564–573
El-Khoury V et al (2016) Assessing cellular and circulating miRNA recovery: the impact of the RNA isolation method and the quantity of input material. Sci Rep 6:19529
Garo LP, Murugaiyan G (2016) Contribution of MicroRNAs to autoimmune diseases. Cell Mol Life Sci 73(10):2041–2051
Garzon R et al (2006) MicroRNA expression and function in cancer. Trends Mol Med 12(12):580–587
Gemmell CH, Sefton MV, Yeo EL (1993) Platelet-derived microparticle formation involves glycoprotein IIb-IIIa. Inhibition by RGDS and a Glanzmann’s thrombasthenia defect. J Biol Chem 268(20):14586–14589
Gilad S et al (2012) Classification of the four main types of lung cancer using a microRNA-based diagnostic assay. J Mol Diagn 14(5):510–517
Haider BA et al (2014) A critical evaluation of microRNA biomarkers in non-neoplastic disease. PLoS ONE 9(2):e89565
Hawkins RC (2010) Phlebotomy site haemolysis rates vary inversely with workload. Clin Chem Lab Med 48(7):1049–1051
He L et al (2005) A microRNA polycistron as a potential human oncogene. Nature 435(7043):828–833
Heitzer E, Ulz P, Geigl JB (2015) Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem 61(1):112–123
Huggett JF et al (2008) Differential susceptibility of PCR reactions to inhibitors: an important and unrecognised phenomenon. BMC Res Notes 1:70
Hunter MP et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE 3(11):e3694
Ishikawa H et al (2017) Stability of serum high-density lipoprotein-microRNAs for preanalytical conditions. Ann Clin Biochem 54(1):134–142
Jarry J et al (2014) The validity of circulating microRNAs in oncology: five years of challenges and contradictions. Mol Oncol 8(4):819–829
Keller S et al (2011) Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med 9:86
Kinoshita T et al (2017) MicroRNAs in extracellular vesicles: potential cancer biomarkers. J Hum Genet 62(1):67–74
Kirschner MB et al (2013) The impact of hemolysis on cell-free microRNA biomarkers. Front Genet 4:94
Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res, 2011. 39(Database issue): p. D152–7
Lance MD et al (2013) Do blood collection methods influence whole-blood platelet function analysis? Platelets 24(4):275–281
Larrea E et al (2016) New concepts in cancer biomarkers: circulating miRNAs in liquid biopsies. Int J Mol Sci, 2016. 17(5)
Lawrie CH 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(5):672–675
Lee YS, Dutta A (2009) MicroRNAs in cancer. Annu Rev Pathol 4:199–227
Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20
Lin S, Gregory RI (2015) MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15(6):321–333
Lippi G et al (2012) Influence of mechanical trauma of blood and hemolysis on PFA-100 testing. Blood Coagul Fibrinolysis 23(1):82–86
Lithwick-Yanai G et al (2017) Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears. J Clin Pathol 70(6):500–507
Lu J et al (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838
Maillot G et al (2009) Widespread estrogen-dependent repression of microRNAs involved in breast tumor cell growth. Cancer Res 69(21):8332–8340
Mall C et al (2013) Stability of miRNA in human urine supports its biomarker potential. Biomark Med 7(4):623–631
McNutt M (2014) Journals unite for reproducibility. Science 346(6210):679
Meiri E et al (2012) A second-generation microRNA-based assay for diagnosing tumor tissue origin. Oncologist 17(6):801–812
Meisgen F et al (2012) MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis. Exp Dermatol 21(4):312–314
Mestdagh P et al (2014) Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study. Nat Methods 11(8):809–815
Meyer SU et al (2012) Profound effect of profiling platform and normalization strategy on detection of differentially expressed microRNAs–a comparative study. PLoS ONE 7(6):e38946
Michael A et al (2010) Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 16(1):34–38
Mitchell PS et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105(30):10513–10518
Negrini M, Nicoloso MS, Calin GA (2009) MicroRNAs and cancer—new paradigms in molecular oncology. Curr Opin Cell Biol 21(3):470–479
Palmer RD et al (2010) Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets. Cancer Res 70(7):2911–2923
Patnaik SK, Mallick R, Yendamuri S (2010) Detection of microRNAs in dried serum blots. Anal Biochem 407(1):147–149
Pentheroudakis G et al (2013) Novel microRNA-based assay demonstrates 92% agreement with diagnosis based on clinicopathologic and management data in a cohort of patients with carcinoma of unknown primary. Mol Cancer 12:57
Qin LX, Tuschl T, Singer S (2013) An empirical evaluation of normalization methods for microRNA arrays in a liposarcoma study. Cancer Inform 12:83–101
Ralla B et al (2014) Nucleic acid-based biomarkers in body fluids of patients with urologic malignancies. Crit Rev Clin Lab Sci 51(4):200–231
Rosenfeld N et al (2008) MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol 26(4):462–469
Schwarzenbach H et al (2015) Data normalization strategies for microRNA quantification. Clin Chem 61(11):1333–1342
Sestini S et al (2015) Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening. Oncotarget 6(32):32868–32877
Shah JS, Soon PS, Marsh DJ (2016) Comparison of methodologies to detect low levels of hemolysis in serum for accurate assessment of serum microRNAs. PLoS ONE 11(4):e0153200
Shaham L et al (2012) MiR-125 in normal and malignant hematopoiesis. Leukemia 26(9):2011–2018
Shkurnikov MY et al (2016) Analysis of plasma microRNA associated with hemolysis. Bull Exp Biol Med 160(6):748–750
Smalheiser NR (2007) Exosomal transfer of proteins and RNAs at synapses in the nervous system. Biol Direct 2:35
Sozzi G et al (2014) Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD trial study. J Clin Oncol 32(8):768–773
Spector Y et al (2013) Development and validation of a microRNA-based diagnostic assay for classification of renal cell carcinomas. Mol Oncol 7(3):732–738
Stark A et al (2003) Identification of drosophila MicroRNA targets. PLoS Biol 1(3):E60
Sun YM, Lin KY, Chen YQ (2013) Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol 6:6
Svoronos AA, Engelman DM, Slack FJ (2016) OncomiR or tumor suppressor? The duplicity of microRNAs in cancer. Cancer Res 76(13):3666–3670
Tiberio P et al (2015) Challenges in using circulating miRNAs as cancer biomarkers. Biomed Res Int 2015:731479
Tuck MK et al (2009) Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res 8(1):113–117
Valadi H et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659
Vickers KC et al (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13(4):423–433
Volinia S et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103(7):2257–2261
Wan JCM et al (2017) Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer 17(4):223–238
Wang D et al (2010) Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: from functions to targets. PLoS One 5(9)
Wang K et al (2010) Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res 38(20):7248–7259
Weber JA et al (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56(11):1733–1741
Williams AE (2008) Functional aspects of animal microRNAs. Cell Mol Life Sci 65(4):545–562
Witwer KW et al (2013) Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2
Witwer KW (2015) Circulating microRNA biomarker studies: pitfalls and potential solutions. Clin Chem 61(1):56–63
Wu K, Li L, Li S (2015) Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies. Tumour Biol 36(3):1973–1981
Yokota M et al (1999) Effects of heparin on polymerase chain reaction for blood white cells. J Clin Lab Anal 13(3):133–140
Zhang H, Li Y, Lai M (2010) The microRNA network and tumor metastasis. Oncogene 29(7):937–948
Zhao Y et al (2010) Evaluation of normalization methods for two-channel microRNA microarrays. J Transl Med 8:69
Zhu W et al (2009) Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes 2:89
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Andersen, G.B., Tost, J. (2020). Circulating miRNAs as Biomarker in Cancer. In: Schaffner, F., Merlin, JL., von Bubnoff, N. (eds) Tumor Liquid Biopsies. Recent Results in Cancer Research, vol 215. Springer, Cham. https://doi.org/10.1007/978-3-030-26439-0_15
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