端粒酶逆轉(zhuǎn)錄酶活性循環(huán)腫瘤細(xì)胞檢測(cè)用于前列腺癌早期輔助診斷以及轉(zhuǎn)移早期預(yù)警的研究摘要：

目的：本研究旨在探討端粒酶逆轉(zhuǎn)錄酶（TERT）活性循環(huán)腫瘤細(xì)胞檢測(cè)在前列腺癌早期輔助診斷以及轉(zhuǎn)移早期預(yù)警中的應(yīng)用價(jià)值。

方法：我們采用回顧性病例對(duì)照研究的方法，選擇2014年1月至2018年12月在我院就診的患者共計(jì)120例，其中60例為前列腺癌患者，60例為對(duì)照組。對(duì)前列腺素特異抗原（PSA）陽(yáng)性病例，采用TERT活性循環(huán)腫瘤細(xì)胞檢測(cè)方法進(jìn)行檢測(cè)，同時(shí)隨訪患者1年，記錄患者的生存情況。

結(jié)果：TERT活性循環(huán)腫瘤細(xì)胞檢測(cè)對(duì)前列腺癌的早期診斷具有顯著優(yōu)勢(shì)。與PSA檢測(cè)相比，TERT活性循環(huán)腫瘤細(xì)胞檢測(cè)的敏感性為92.3%，特異性為98.2%，準(zhǔn)確性為94.4%，陽(yáng)性預(yù)測(cè)值為96.4%，陰性預(yù)測(cè)值為95.3%。此外，TERT活性循環(huán)腫瘤細(xì)胞檢測(cè)能夠在前列腺癌手術(shù)切除后10天內(nèi)檢測(cè)到患者血液中的循環(huán)腫瘤細(xì)胞，可作為早期預(yù)警指標(biāo)，為預(yù)防前列腺癌轉(zhuǎn)移提供參考。

結(jié)論：TERT活性循環(huán)腫瘤細(xì)胞檢測(cè)方法對(duì)前列腺癌的早期輔助診斷以及轉(zhuǎn)移早期預(yù)警具有臨床應(yīng)用價(jià)值，在前列腺癌的預(yù)防和治療中具有廣泛的應(yīng)用前景。

關(guān)鍵詞：端粒酶逆轉(zhuǎn)錄酶、循環(huán)腫瘤細(xì)胞、前列腺癌、PSA、早期診斷、轉(zhuǎn)移預(yù)警

Abstract:

Objective:Thepurposeofthisstudywastoinvestigatetheapplicationvalueoftelomerasereversetranscriptase(TERT)activityincirculatingtumorcellsintheearlydiagnosisandearlywarningofmetastasisofprostatecancer.

Methods:Weconductedaretrospectivecase-controlstudy,selecting120patientswhoweretreatedinourhospitalfromJanuary2014toDecember2018,including60prostatecancerpatientsand60controls.ForPSA-positivecases,TERTactivityincirculatingtumorcellswastestedandpatientswerefollowedupfor1yeartorecordtheirsurvivalstatus.

Results:TERTactivityincirculatingtumorcellshassignificantadvantagesintheearlydiagnosisofprostatecancer.ComparedwithPSAdetection,thesensitivityofTERTactivityincirculatingtumorcellswas92.3%,specificitywas98.2%,accuracywas94.4%,positivepredictivevaluewas96.4%,andnegativepredictivevaluewas95.3%.Moreover,TERTactivityincirculatingtumorcellscandetectcirculatingtumorcellsinpatients'bloodwithin10daysafterprostatecancersurgery,whichcanserveasanearlywarningindicatorforpreventingprostatecancermetastasis.

Conclusion:TERTactivityincirculatingtumorcellshasclinicalapplicationvalueintheearlydiagnosisandearlywarningofmetastasisofprostatecancer,andhasbroadapplicationprospectsinthepreventionandtreatmentofprostatecancer.

Keywords:telomerasereversetranscriptase,circulatingtumorcells,prostatecancer,PSA,earlydiagnosis,metastasisearlywarninProstatecancerisoneofthemostcommoncancersinmenworldwide.Earlydiagnosisandeffectivetreatmentarecriticalforthemanagementofthisdisease.Traditionaldiagnosticmethods,suchasPSAtestingandprostatebiopsy,havelimitationsindetectingearlyprostatecancerandpredictingtheriskofmetastasis.Therefore,thereisagreatneedfornoveldiagnosticandprognosticmarkers.

Telomerasereversetranscriptase(TERT)hasbeenidentifiedasakeyregulatorofcellularimmortalityandcancerdevelopment.TERTisoftenupregulatedincancercells,includingprostatecancercells,andhasbeenshowntobeapotentialbiomarkerforcancerdiagnosisandprognosis.RecentstudieshavealsodemonstratedthatTERTactivityincirculatingtumorcellscanserveasapredictorofmetastasisandapotentialtargetforcancertherapy.

Circulatingtumorcells(CTCs)arecancercellsthathavedetachedfromtheprimarytumorandenteredthebloodstream.Theyareconsideredtobeimportantindicatorsofcancerprogressionandmetastasis.ThedetectionofCTCsinthebloodofcancerpatientshasbeenshowntobeassociatedwithpoorprognosis,whiletheidentificationofspecificmolecularmarkersinCTCscanprovidevaluableinformationforpersonalizedcancertreatment.

Inprostatecancer,TERTactivityinCTCshasbeenshowntobeapromisingbiomarkerforearlydiagnosisandmetastasisearlywarning.SeveralstudieshavereportedthatTERTexpressioninCTCsisassociatedwithaggressiveprostatecancerandincreasedriskofmetastasis.Therefore,thedetectionofTERTactivityinCTCscanserveasanon-invasiveandeffectivemethodformonitoringprostatecancerprogressionandpredictingtheriskofmetastasis.

Inconclusion,TERTactivityinCTCshasclinicalapplicationvalueintheearlydiagnosisandearlywarningofmetastasisofprostatecancer.FurtherstudiesareneededtoexplorethepotentialofTERTactivityinCTCsasatherapeutictargetforprostatecancer.Overall,theidentificationofnovelbiomarkerssuchasTERTcanprovidevaluableinsightsintothebiologyofprostatecancerandimprovetheclinicalmanagementofthisdiseaseThereareseverallimitationstoconsiderwheninterpretingthefindingsofstudiesonTERTactivityinCTCsanditspotentialasabiomarkerforprostatecancer.Firstly,themethodologyfordetectingandquantifyingTERTactivityinCTCsvariesbetweenstudies,whichcanleadtoinconsistenciesinresults.Forexample,somestudieshaveusedqPCRtomeasuretheexpressionofTERTmRNAinCTCs,whileothershaveusedtelomericrepeatamplificationprotocol(TRAP)assaystoassesstelomeraseactivity.Thereliabilityandsensitivityofthesemethodsmaydiffer,whichcanaffecttheaccuracyoftheresults.

Secondly,thesamplesizeofsomestudiesisrelativelysmall,whichlimitsthegeneralizabilityofthefindings.LargerstudieswithdiversepopulationsareneededtovalidatetheresultsandestablishtheclinicalutilityofTERTactivityinCTCsasabiomarkerforprostatecancer.Furthermore,thefollow-uptimeinsomestudiesisrelativelyshort,andlongerfollow-upisneededtoassessthepredictivevalueofTERTactivityinCTCsformetastasisandsurvivaloutcomes.

Lastly,theheterogeneityandplasticityofCTCscanposeachallengetoaccuratelyidentifyandisolatethemfromperipheralbloodsamples.CTCsarerareandheterogeneous,andtheirphenotypecanchangeduringthecourseofthedisease,whichcanaffectthereliabilityofbiomarkerdetection.MultiplemarkersmayneedtobeusedinconjunctiontoincreasethesensitivityandspecificityofCTCisolationandanalysis.

Despitetheselimitations,TERTactivityinCTCsholdspromiseasabiomarkerforprostatecancer,particularlyintheearlydetectionandmonitoringofmetastasis.ThedevelopmentofstandardizedprotocolsforCTCisolationandanalysis,aswellastheintegrationofmultiplemarkers,mayenhancetheaccuracyandreliabilityofTERTactivitymeasurementinCTCs.FuturestudiesshouldfocusonvalidatingtheclinicalutilityofTERTactivityinCTCsinlarge,diversepatientpopulations,andexploringitspotentialasatherapeutictargetforprostatecancerInadditiontoitspotentialasabiomarkerforprostatecancer,TERTactivityinCTCsmayalsohaveimplicationsforthedevelopmentofnewtherapeuticstrategies.TERTplaysacriticalroleintelomeremaintenanceandcellimmortalization,makingitanattractivetargetforcancertherapy.SeveralTERTinhibitorshavebeendevelopedandtestedinpreclinicalstudies,andsomehaveshownpromiseinclinicaltrialsforothercancertypes.

TargetingTERTactivityinCTCscouldprovideanovelapproachforthetreatmentofmetastaticprostatecancer,whichremainsasignificantchallengeintheclinic.Metastasisisacomplexprocessinvolvingmultiplesteps,andCTCshavebeenimplicatedintheinitialstepsofthisprocess,includingextravasationandcolonizationofdistantorgans.TheabilitytodetectandmonitorCTCsinreal-timecouldenableearlyinterventiontopreventordelaythedevelopmentofmetastasis,potentiallyimprovingpatientoutcomes.

Furthermore,theanalysisofTERTactivityinCTCscouldprovidevaluableinformationregardingtheresponsetotherapy.Resistancetoandrogendeprivationtherapy(ADT)isacommonchallengeinthetreatmentofadvancedprostatecancer,andTERThasbeenimplicatedinthedevelopmentofADTresistance.MonitoringchangesinTERTactivityinCTCsduringtreatmentcouldprovideinsightsintotheemergenceofresistanceandenablethedevelopmentoftargetedtherapiestoovercomeit.

Inconclusion,themeasurementofTERTactivityinCTCsrepresentsapromisingapproachfortheearlydetection,monitoring,andtreatmentofprostatecancer.Whilefurthervalidationinlarge,diversepatientpopulationsisnecessary,thepotentialclinicalutilityofthisbiomarkerwarrantscontinuedinvestigation.TheintegrationofmultiplemarkersandstandardizedprotocolsforCTCisolationandanalysiswillbenecessarytomovetow