Cell-free nucleic acids as biomarkers

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1、REVIEWSCell-freenucleicacidsasbiomarkersincancerpatientsHeidiSchwarzenbach*,DaveS. B. Hoon‡andKlausPantel*Abstract

2、DNA,mRNAandmicroRNAarereleasedandcirculateinthebloodofcancerpatients.Changesinthelevelsofcirculatingnucleicacidshavebeenassociatedwithtumourburdenandmalignantprogr

3、ession.Inthepastdecadeawealthofinformationindicatingthepotentialuseofcirculatingnucleicacidsforcancerscreening,prognosisandmonitoringoftheefficacyofanticancertherapieshasemerged.InthisReview,wediscussthesefindingswithaspecificfocusontheclinicalutilityofcell-freenucleicacidsasbl

4、oodbiomarkers.In1948,MandelandMétais1describedthepresenceofThisReviewfocusesontheclinicalutilityofcfNA,microRNAsSmallnon-codingRNAcell-freenucleicacid(cfNA)inhumanbloodforthefirstincludinggeneticandepigeneticalterationsthatcanmoleculesthatmodulatethetime.Thisattractedlittleatte

5、ntioninthescientificcom-bedetectedincfDNA,aswellasthequantificationofactivityofspecificmRNAmunityanditwasnotuntil1994thattheimportancenucleosomesandmiRNAs,anddiscussestherelationshipmoleculesbybindingandofcfNAwasrecognizedasaresultofthedetectionofbetweencfNAandmicrometastatic c

6、ells.inhibitingtheirtranslationintomutatedRASgenefragmentsinthebloodofcancerpolypeptides.patients2,3(TIMELINE).In1996,microsatellitealtera-BiologyofcfNAtionsoncell-freeDNA(cfDNA)wereshownincancerThereleaseofnucleicacidsintothebloodisthoughttopatients4,andduringthepastdecadeincr

7、easingatten-berelatedtotheapoptosisandnecrosisofcancercellstionhasbeenpaidtocfNAs(suchasDNA,mRNAandinthetumourmicroenvironment.SecretionhasalsomicroRNAs(miRNAs))thatarepresentathighconcentra-beensuggestedasapotentialsourceofcfDNA(FIG. 1).tionsinthebloodofcancerpatients(FIG. 1).

8、Indeed,theirNecroticandapoptoticcellsareusuallyphagocytosedpotentialvalueasbloodbiomarkerswashighlightedinabymacrophagesorotherscavengercells8.MacrophagesrecenteditorialinthejournalScience5.thatengulfnecroticcellscanreleasedigestedDNAintoDetectingcfNAinplasmaorserumcouldserveas

9、thetissueenvironment.In vitrocellcultureexperimentsa‘l