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RESEARCH PRODUCT
Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients
Frank BertholdFrank SpelemanAna P. BerbegallKatrien VanderheydenJulie Bienertova VaskuMatthias FischerMatthias FischerShifra AshJo VandesompeleMichael D. HogartyFleur DemuynckFjoralba ZekaSven RahmannJohannes H. SchulteJohannes H. SchulteJohannes H. SchulteJoëlle VermeulenMarta JeisonRosa NogueraGudrun SchleiermacherJason M. ShohetPieter MestdaghGenevieve LaureysGenevieve LaureysAlan Van GoethemTom Van MaerkenEveline BarbieriMirthala Moreno-smithAnneleen DecockKatleen De PreterHetty HelsmoortelAlexander SchrammValérie CombaretPavel MazánekTim LammensTim Lammenssubject
AdultMale0301 basic medicineOncologymedicine.medical_specialtyAdolescentTransplantation HeterologousMedizinDiseaseMiceNeuroblastomaYoung Adult03 medical and health sciencesInternal medicineNeuroblastomamicroRNABiomarkers TumormedicineAnimalsHumansCirculating MicroRNANeoplasm MetastasisStage (cooking)ChildAgedNeoplasm StagingNoninvasive biomarkersAged 80 and overbusiness.industryGeneral MedicineMiddle AgedSerum samplesmedicine.diseaseMicroRNAsCirculating MicroRNA030104 developmental biologyChild PreschoolLocalized diseaseFemalebusinessResearch Articledescription
In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response. CA extern
year | journal | country | edition | language |
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2018-01-01 |