Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients

被引：25

作者：

Zeka, Fjoralba ^{[1
,2
]}

Decock, Anneleen ^{[1
,2
]}

Van Goethem, Alan ^{[1
,2
]}

Vanderheyden, Katrien ^{[1
,2
]}

Demuynck, Fleur ^{[1
]}

Lammens, Tim ^{[2
,3
]}

Helsmoortel, Hetty H. ^{[1
,2
]}

Vermeulen, Joelle ^{[4
]}

Noguera, Rosa ^{[5
]}

Berbegall, Ana P. ^{[5
,6
]}

Combaret, Valerie ^{[7
]}

Schleiermacher, Gudrun ^{[8
]}

Laureys, Genevieve ^{[2
,3
]}

Schramm, Alexander ^{[9
]}

Schulte, Johannes H. ^{[9
,10
,11
]}

Rahman, Sven ^{[12
]}

Bienertova-Vasku, Julie ^{[13
]}

Mazanek, Pavel ^{[13
]}

Jeison, Marta ^{[14
]}

Ash, Shifra ^{[14
]}

Hogarty, Michael D. ^{[15
]}

Moreno-Smith, Mirthala ^{[16
]}

Barbieri, Eveline ^{[16
]}

Shohet, Jason ^{[16
]}

Berthold, Frank ^{[17
]}

Van Maerken, Tom ^{[1
,2
]}

Speleman, Frank ^{[1
,2
]}

Fischer, Matthias ^{[17
,18
]}

De Preter, Katleen ^{[1
,2
]}

Mestdagh, Pieter ^{[1
,2
]}

Vandesompele, Jo ^{[1
,2
]}

机构：

[1] Univ Ghent, Ctr Med Genet, Dept Biomol Med, Ghent, Belgium

[2] Univ Ghent, CRIG, Ghent, Belgium

[3] Ghent Univ Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Ghent, Belgium

[4] Hop Jolimont, Pediat, Haine St Paul, Belgium

[5] Univ Valencia, CIBERONC Madrid, Dept Pathol, Med Sch, Valencia, Spain

[6] INCLIVA Biomed Res Inst, Valencia, Spain

[7] Ctr Leon Berard, Lab Rech Translat, Lyon, France

[8] Inst Curie, Dept Paediat Oncol, Paris, France

[9] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Mol Oncol, Essen, Germany

[10] Charite, Pediat Oncol & Hematol, Berlin, Germany

[11] German Canc Consortium DKTK, German Canc Res Ctr DKFZ, Heidelberg, Germany

[12] Univ Duisburg Essen, Univ Hosp Essen, Inst Human Genet, Genome Informat, Essen, Germany

[13] Univ Hosp Brno, Dept Pediat Oncol, Brno, Czech Republic

[14] Schneider Childrens Med Ctr Israel, Pediat Hematol Oncol, Tel Aviv, Israel

[15] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[16] Baylor Coll Med, Dept Pediat, Sect Hematol Oncol, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[17] Univ Cologne, Univ Childrens Hosp Cologne, Med Fac, Pediat Oncol & Hematol, Cologne, Germany

[18] Univ Cologne, CMMC, Cologne, Germany

来源：

JCI INSIGHT | 2018年 / 3卷 / 23期

关键词：

SERUM; EXPRESSION; DNA; CHILDHOOD; QUALITY;

D O I：

10.1172/jci.insight.97021

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：13

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