Extracellular RNAs as potential biomarkers for cancer

Christine Happel , Aniruddha Ganguly , Danilo A. Tagle

Journal of Cancer Metastasis and Treatment ›› 2020, Vol. 6 : 32

PDF
Journal of Cancer Metastasis and Treatment ›› 2020, Vol. 6:32 DOI: 10.20517/2394-4722.2020.71
Review
review-article

Extracellular RNAs as potential biomarkers for cancer

Author information +
History +
PDF

Abstract

The discovery that all cells secrete extracellular vesicles (EVs) to shuttle proteins and nucleic acids to recipient cells suggested they play an important role in intercellular communication. EVs are widely distributed in many body fluids, including blood, cerebrospinal fluid, urine and saliva. Exosomes are nano-sized EVs of endosomal origin that regulate many pathophysiological processes including immune responses, inflammation, tumour growth, and infection. Healthy individuals release exosomes with a cargo of different RNA, DNA, and protein contents into the circulation, which can be measured non-invasively as biomarkers of healthy and diseased states. Cancer-derived exosomes carry a unique set of DNA, RNA, protein and lipid reflecting the stage of tumour progression, and may serve as diagnostic and prognostic biomarkers for various cancers. However, many gaps in knowledge and technical challenges in EVs and extracellular RNA (exRNA) biology, such as mechanisms of EV biogenesis and uptake, exRNA cargo selection, and exRNA detection remain. The NIH Common Fund-supported exRNA Communication Consortium was launched in 2013 to address major scientific challenges in this field. This review focuses on scientific highlights in biomarker discovery of exosome-based exRNA in cancer and its possible clinical application as cancer biomarkers.

Keywords

Extracellular vesicles / exosomes / extracellular RNA / cancer / biomarker / liquid biopsy

Cite this article

Download citation ▾
Christine Happel, Aniruddha Ganguly, Danilo A. Tagle. Extracellular RNAs as potential biomarkers for cancer. Journal of Cancer Metastasis and Treatment, 2020, 6: 32 DOI:10.20517/2394-4722.2020.71

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Skog J,van Rijn S,Gainche L.Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers..Nat Cell Biol2008;10:1470-6 PMCID:PMC3423894

[2]

Valadi H,Bossios A,Lee JJ.Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells..Nat Cell Biol2007;9:654-9

[3]

Iorio MV.MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review..EMBO Mol Med2012;4:143-59 PMCID:PMC3376845

[4]

Godoy PM,Barczak AJ,Fisher S.Large Differences in small RNA Composition between human biofluids..Cell Rep2018;25:1346-58 PMCID:PMC6261476

[5]

Yeri A,Reiman R,Beecroft T.Total extracellular small RNA profiles from plasma, saliva, and urine of healthy subjects..Sci Rep2017;7:44061 PMCID:PMC5356006

[6]

Saugstad JA,Van Keuren-Jensen KR,Lind B.Analysis of extracellular RNA in cerebrospinal fluid..J Extracell Vesicles2017;6:1317577 PMCID:PMC5505019

[7]

Lasser C,Ekstrom K,Paredes PT.Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages..J Transl Med2011;9:9 PMCID:PMC3033821

[8]

Freedman JE,Mick E,Levy D.Diverse human extracellular RNAs are widely detected in human plasma..Nat Commun2016;7:11106 PMCID:PMC4853467

[9]

Mittelbrunn M,Villarroya-Beltri C,Sanchez-Cabo F.Unidirectional transfer of microRNA-loaded exosomes from t cells to antigen-presenting cells..Nat Commun2011;2:282 PMCID:PMC3104548

[10]

Pegtel DM,Thorley-Lawson DA,Hopmans ES.Functional delivery of viral miRNAs via exosomes..Proc Natl Acad Sci U S A2010;107:6328-33 PMCID:PMC2851954

[11]

Balaj L,Dai L,Pomeroy SL.Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences..Nat Commun2011;2:180 PMCID:PMC3040683

[12]

Colombo M,Thery C.Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles..Annu Rev Cell Dev Biol2014;30:255-89

[13]

van Niel G,Raposo G.Shedding light on the cell biology of extracellular vesicles..Nat Rev Mol Cell Biol2018;19:213-28

[14]

Chen X,Ma L,Yin Y.Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases..Cell Res2008;18:997-1006

[15]

Mitchell PS,Kroh EM,Wyman SK.Circulating microRNAs as stable blood-based markers for cancer detection..Proc Natl Acad Sci U S A2008;105:10513-8 PMCID:PMC2492472

[16]

Tabet F,Cuesta Torres LF,Shoucri BM.HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells..Nat Commun2014;5:3292 PMCID:PMC4189962

[17]

Vickers KC,Shoucri BM,Remaley AT.MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins..Nat Cell Biol2011;13:423-33 PMCID:PMC3074610

[18]

Quinn JF,Wong D,Freedman JE.Extracellular RNAs: development as biomarkers of human disease..J Extracell Vesicles2015;4:27495 PMCID:PMC4553262

[19]

Lombo TB,Tagle DA.Diagnostic potential of extracellular RNA from biofluids..Expert Rev Mol Diagn2016;16:1135-8

[20]

Siravegna G,Siena S.Integrating liquid biopsies into the management of cancer..Nat Rev Clin Oncol2017;14:531-48

[21]

Heitzer E,Roberts CES.Current and future perspectives of liquid biopsies in genomics-driven oncology..Nat Rev Genet2019;20:71-88

[22]

Wang JY,Chang MY,Chen FM.Molecular detection of APC, K-ras, and p53 mutations in the serum of colorectal cancer patients as circulating biomarkers..World J Surg2004;28:721-6

[23]

Diaz LA Jr.Liquid biopsies: genotyping circulating tumor DNA..J Clin Oncol2014;32:579-86 PMCID:PMC4820760

[24]

Haber DA.Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA..Cancer Discov2014;4:650-61 PMCID:PMC4433544

[25]

Yu M,Toner M,Haber DA.Circulating tumor cells: approaches to isolation and characterization..J Cell Biol2011;192:373-82 PMCID:PMC3101098

[26]

Schwarzenbach H,Pantel K.Detection and monitoring of cell-free DNA in blood of patients with colorectal cancer..Ann N Y Acad Sci2008;1137:190-6

[27]

Neumann MHD,Krahn T.ctDNA and CTCs in liquid biopsy-current status and where we need to progress..Comput Struct Biotechnol J2018;16:190-5 PMCID:PMC6024152

[28]

Tirosh I,Prakadan SM,Treacy D.Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq..Science2016;352:189-96 PMCID:PMC4944528

[29]

Ramalingam N.Future of liquid biopsies with growing technological and bioinformatics studies: opportunities and challenges in discovering tumor heterogeneity with single-cell level analysis..Cancer J2018;24:104-8 PMCID:PMC5880298

[30]

De Mattos-Arruda L,Cortes J,Ng CK.Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle..Ann Oncol2014;25:1729-35 PMCID:PMC6276937

[31]

De Mattos-Arruda L,Ng CKY,Martinez-Ricarte F.Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma..Nat Commun2015;6:8839 PMCID:PMC5426516

[32]

Murtaza M,Pogrebniak K,Provenzano E.Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer..Nat Commun2015;6:8760 PMCID:PMC4659935

[33]

Ulz P,Auer M,Kashofer K.Inferring expressed genes by whole-genome sequencing of plasma DNA..Nat Genet2016;48:1273-8

[34]

Laterza OF,Garrett-Engele PW,Muniappa N.Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury..Clin Chem2009;55:1977-83

[35]

Lu J,Miska EA,Lamb J.MicroRNA expression profiles classify human cancers..Nature2005;435:834-8

[36]

Driedonks TAP.Circulating y-RNAs in extracellular vesicles and ribonucleoprotein complexes; implications for the immune system..Front Immunol2018;9:3164 PMCID:PMC6340977

[37]

Argyropoulos C,McClarty S,Bernardo J.Urinary microRNA profiling in the nephropathy of type 1 diabetes..PLoS One2013;8:e54662 PMCID:PMC3554645

[38]

Fujita Y,Ochiya T.The impact of extracellular vesicle-encapsulated circulating microRNAs in lung cancer research..Biomed Res Int2014;2014:486413 PMCID:PMC4176915

[39]

Inns J.Circulating microRNAs for the prediction of metastasis in breast cancer patients diagnosed with early stage disease..Breast2015;24:364-9

[40]

Duijvesz D,Bangma CH.Exosomes as biomarker treasure chests for prostate cancer..Eur Urol2011;59:823-31

[41]

Huang X,Liang M,Xia S.Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer..Eur Urol2015;67:33-41 PMCID:PMC4252606

[42]

McDonald JS,Reddi HV,Algeciras-Schimnich A.Analysis of circulating microRNA: preanalytical and analytical challenges..Clin Chem2011;57:833-40

[43]

Akers JC,Yang I,Mao Y.Optimizing preservation of extracellular vesicular miRNAs derived from clinical cerebrospinal fluid..Cancer Biomark2016;17:125-32 PMCID:PMC4992418

[44]

O’Neill CP,Dwyer RM.Role of extracellular vesicles (EVs) in cell stress response and resistance to cancer therapy..Cancers (Basel)2019;11:136 PMCID:PMC6406503

[45]

Mehta S,Muthukaruppan A,Blenkiron C.Predictive and prognostic molecular markers for cancer medicine..Ther Adv Med Oncol2010;2:125-48 PMCID:PMC3126011

[46]

FDA-NIH biomarker working groupBEST (Biomarkers, endpoints, and other tools) resource.2016;Silver spring (MD)food and drug administration

[47]

Food and drug administration. CDER biomarker qualification program. Available from: https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/cder-biomarker-qualification-program. [Last accessed on 7 May 2020]

[48]

Amur SG,Chakravarty AG,Kaiser J.Building a roadmap to biomarker qualification: challenges and opportunities..Biomark Med2015;9:1095-105

[49]

Laurent LC,Adelson PD,Balaj L.Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH extracellular RNA communication consortium..J Extracell Vesicles2015;4:26533 PMCID:PMC4553263

[50]

McKiernan J,O’Neill V,Noerholm M.A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy..JAMA Oncol2016;2:882-9

[51]

Li F,Kim KM,Grogan TR.Discovery and validation of salivary extracellular RNA biomarkers for noninvasive detection of gastric cancer..Clin Chem2018;64:1513-21

[52]

Mithraprabhu S,Khong T,Bergin K.Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients..Leukemia2019;33:2022-33

[53]

Castellanos-Rizaldos E,Tadigotla V,Healy J.Exosome-based detection of EGFR T790M in plasma from non-small cell lung cancer patients..Clin Cancer Res2018;24:2944-50

[54]

Castellanos-Rizaldos E,Tadigotla VR,Karlovich C.Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients..Oncotarget2019;10:2911-20 PMCID:PMC6499599

[55]

U.S. National Library of Medicine. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/. [Last accessed on 3 Sep 2020]

[56]

Lee YH.Saliva: an emerging biofluid for early detection of diseases..Am J Dent2009;22:241-8 PMCID:PMC2860957

[57]

Slavkin HC.Toward molecularly based diagnostics for the oral cavity..J Am Dent Assoc1998;129:1138-43

[58]

Donovan MJ,Bentink S,Skog J.A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result..Prostate Cancer Prostatic Dis2015;18:370-5

[59]

Tutrone R,Torkler P,McLain T.Clinical utility of the exosome based exodx prostate(intelliScore) EPI test in men presenting for initial biopsy with a PSA 2-10 ng/mL..Prostate Cancer Prostatic Dis2020;doi: 10.1038/s41391-020-0237-z

[60]

Abels ER.Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake..Cell Mol Neurobiol2016;36:301-12 PMCID:PMC5546313

[61]

Li K,Kashanchi F,Gould SJ.Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA strategic workshop..JCI Insight2018;3:e98942 PMCID:PMC5928855

[62]

Galvanin A,Ayadi L,Velot E.Diversity and heterogeneity of extracellular RNA in human plasma..Biochimie2019;164:22-36

[63]

Minciacchi VR,Di Vizio D.Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes..Semin Cell Dev Biol2015;40:41-51 PMCID:PMC4747631

[64]

Simonsen JB.What are we looking at? extracellular vesicles, lipoproteins, or both?.Circ Res2017;121:920-2

[65]

Murillo OD,Rozowsky J,Lucero R.exRNA atlas analysis reveals distinct extracellular RNA cargo types and their carrierspresent across human biofluids..Cell2019;177:463-77.e15 PMCID:PMC6616370

[66]

Mulcahy LA,Carter DR.Routes and mechanisms of extracellular vesicle uptake..J Extracell Vesicles2014;3: PMCID:PMC4122821

[67]

Parolini I,Raggi C,Palleschi S.Microenvironmental pH is a key factor for exosome traffic in tumor cells..J Biol Chem2009;284:34211-22 PMCID:PMC2797191

[68]

Das S,Bitzer M,Charest A.The extracellular RNA communication consortium: establishingfoundational knowledge and technologies for extracellular RNA research..Cell2019;177:231-42 PMCID:PMC6601620

[69]

Srinivasan S,Cheah PS,Danielson K.Small RNA sequencing across diverse biofluids identifies optimal methods for exRNA isolation..Cell2019;177:446-62 e16 PMCID:PMC6557167

[70]

Zaborowski MP,Na YJ,Zhang X.Methods for systematic identification of membrane proteins for specific capture of cancer-derived extracellular vesicles..Cell Rep2019;27:255-68.e6 PMCID:PMC6528836

[71]

Akat KM,Morozov P,Gogakos T.Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers..Proc Natl Acad Sci U S A2014;111:11151-6 PMCID:PMC4121804

[72]

Lambert M,Provost P.Small non-coding RNAs derived from eukaryotic ribosomal RNA..Noncoding RNA2019;5:16 PMCID:PMC6468398

[73]

Keam SP.tRNA-derived fragments (tRFs): emerging new roles for an ancient RNA in the regulation of gene expression..Life (Basel)2015;5:1638-51 PMCID:PMC4695841

[74]

Valadkhan S.Role of small nuclear RNAs in eukaryotic gene expression..Essays Biochem2013;54:79-90

[75]

Bachellerie JP,Huttenhofer A.The expanding snoRNA world..Biochimie2002;84:775-90

[76]

Liang J,Huang Z,Zhang BX.Small nucleolar RNAs: insight into their function in cancer..Front Oncol2019;9:587 PMCID:PMC6629867

[77]

Schimmel P.The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis..Nat Rev Mol Cell Biol2018;19:45-58

[78]

Flintoft L.Non-coding RNA: structure and function for lncRNAs..Nat Rev Genet2013;14:598

[79]

Bartel DP.MicroRNAs: genomics, biogenesis, mechanism, and function..Cell2004;116:281-97

[80]

Krol J,Filipowicz W.The widespread regulation of microRNA biogenesis, function and decay..Nat Rev Genet2010;11:597-610

[81]

Ozata DM,Zoch A,Zamore PD.PIWI-interacting RNAs: small RNAs with big functions..Nat Rev Genet2019;20:89-108

[82]

Dana H,Mahmoodzadeh H,Rezaiean O.Molecular Mechanisms and Biological Functions of siRNA..Int J Biomed Sci2017;13:48-57 PMCID:PMC5542916

[83]

Lee YS,Malhotra A.A novel class of small RNAs: tRNA-derived RNA fragments (tRFs)..Genes Dev2009;23:2639-49 PMCID:PMC2779758

[84]

Kowalski MP.Functional roles of non-coding Y RNAs..Int J Biochem Cell Biol2015;66:20-9 PMCID:PMC4726728

AI Summary AI Mindmap
PDF

21

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/