miRNA Expression Profiling Enables Risk Stratification in Archived and Fresh Neuroblastoma Tumor Samples

被引：68

作者：

De Preter, Katleen ^{[1
]}

Mestdagh, Pieter ^{[1
]}

Vermeulen, Joelle ^{[1
]}

Zeka, Fjoralba ^{[1
]}

Naranjo, Arlene ^{[3
]}

Bray, Isabella ^{[4
,5
]}

Castel, Victoria ^{[6
]}

Chen, Caifu ^{[8
]}

Drozynska, Elzbieta ^{[9
]}

Eggert, Angelika ^{[10
]}

Hogarty, Michael D. ^{[11
]}

Ewalzycka-Swieszewska ^{[9
]}

London, Wendy B. ^{[12
]}

Noguera, Rosa ^{[7
]}

Piqueras, Marta ^{[7
]}

Bryan, Kenneth ^{[4
,5
]}

Schowe, Benjamin ^{[13
]}

van Sluis, Peter ^{[14
]}

Molenaar, Jan J. ^{[14
]}

Schramm, Alexander ^{[10
]}

Schulte, Johannes H. ^{[10
]}

Stallings, Raymond L. ^{[4
,5
]}

Versteeg, Rogier ^{[14
]}

Laureys, Genevieve ^{[2
]}

Van Roy, Nadine ^{[1
]}

Speleman, Frank ^{[1
]}

Vandesompele, Jo ^{[1
]}

机构：

[1] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium

[2] Ghent Univ Hosp, Dept Paediat Hematol & Oncol, B-9000 Ghent, Belgium

[3] Univ Florida, Childrens Oncol Grp, Gainesville, FL USA

[4] Royal Coll Surgeons Ireland, Dept Canc Genet, Dublin 2, Ireland

[5] Natl Childrens Res Ctr, Dublin, Ireland

[6] Hosp La Fe, Pediat Oncol Unit, E-46009 Valencia, Spain

[7] Univ Valencia, Dept Pathol, Sch Med, Valencia, Spain

[8] Appl Biosyst Inc, Foster City, CA 94404 USA

[9] Med Univ Gdansk, Dept Pediat Haematol Oncol & Endocrinol, Gdansk, Poland

[10] Univ Childrens Hosp Essen, Dept Pediat Oncol & Haematol, Essen, Germany

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

[12] Childrens Hosp Boston, Childrens Oncol Grp, Dana Farber Harvard Canc Ctr, Boston, MA USA

[13] Tech Univ Dortmund, Dept Comp Sci, Dortmund, Germany

[14] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1105 AZ Amsterdam, Netherlands

来源：

CLINICAL CANCER RESEARCH | 2011年 / 17卷 / 24期

基金：

爱尔兰科学基金会;

关键词：

GENE-EXPRESSION; PREDICTION; CLASSIFICATION; AMPLIFICATION; PROGNOSIS; NETWORKS; RNA;

D O I：

10.1158/1078-0432.CCR-11-0610

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples. Experimental Design: Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples. Results: The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples. Conclusions: In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material. Clin Cancer Res; 17(24); 7684-92. (C)2011 AACR.

引用

页码：7684 / 7692

页数：9

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