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

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2011 Oct 28

PMID 22031095

Citations 44

Authors

Katleen De Preter

Pieter Mestdagh

Joelle Vermeulen

Fjoralba Zeka

Arlene Naranjo

Isabella Bray

Victoria Castel

Caifu Chen

Elzbieta Drozynska

Angelika Eggert

Michael D Hogarty

Ewa Izycka-Swieszewska

Wendy B London

Rosa Noguera

Marta Piqueras

Kenneth Bryan

Benjamin Schowe

Peter van Sluis

Jan J Molenaar

Alexander Schramm

Johannes H Schulte

Raymond L Stallings

Rogier Versteeg

Genevieve Laureys

Nadine Van Roy

Frank Speleman

Jo Vandesompele

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Chen Y, Stallings R . Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 2007; 67(3):976-83. DOI: 10.1158/0008-5472.CAN-06-3667. View

Vermeulen J, De Preter K, Naranjo A, Vercruysse L, Van Roy N, Hellemans J . Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study. Lancet Oncol. 2009; 10(7):663-71. PMC: 3045079. DOI: 10.1016/S1470-2045(09)70154-8. View

Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F . A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009; 10(6):R64. PMC: 2718498. DOI: 10.1186/gb-2009-10-6-r64. View

Wei J, Greer B, Westermann F, Steinberg S, Son C, Chen Q . Prediction of clinical outcome using gene expression profiling and artificial neural networks for patients with neuroblastoma. Cancer Res. 2004; 64(19):6883-91. PMC: 1298184. DOI: 10.1158/0008-5472.CAN-04-0695. View

Mestdagh P, Fredlund E, Pattyn F, Schulte J, Muth D, Vermeulen J . MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. Oncogene. 2009; 29(9):1394-404. DOI: 10.1038/onc.2009.429. View

Fontana L, Fiori M, Albini S, Cifaldi L, Giovinazzi S, Forloni M . Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One. 2008; 3(5):e2236. PMC: 2375057. DOI: 10.1371/journal.pone.0002236. View

Schramm A, Schulte J, Klein-Hitpass L, Havers W, Sieverts H, Berwanger B . Prediction of clinical outcome and biological characterization of neuroblastoma by expression profiling. Oncogene. 2005; 24(53):7902-12. DOI: 10.1038/sj.onc.1208936. View

Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E . Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet. 2006; 38(9):1060-5. PMC: 2669546. DOI: 10.1038/ng1855. View

De Preter K, Vermeulen J, Brors B, Delattre O, Eggert A, Fischer M . Accurate outcome prediction in neuroblastoma across independent data sets using a multigene signature. Clin Cancer Res. 2010; 16(5):1532-41. DOI: 10.1158/1078-0432.CCR-09-2607. View

10.

Tibshirani R, Hastie T, Narasimhan B, Chu G . Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci U S A. 2002; 99(10):6567-72. PMC: 124443. DOI: 10.1073/pnas.082099299. View

11.

Lefever S, Hellemans J, Pattyn F, Przybylski D, Taylor C, Geurts R . RDML: structured language and reporting guidelines for real-time quantitative PCR data. Nucleic Acids Res. 2009; 37(7):2065-9. PMC: 2673419. DOI: 10.1093/nar/gkp056. View

12.

Ruschhaupt M, Huber W, Poustka A, Mansmann U . A compendium to ensure computational reproducibility in high-dimensional classification tasks. Stat Appl Genet Mol Biol. 2006; 3:Article37. DOI: 10.2202/1544-6115.1078. View

13.

Schulte J, Schowe B, Mestdagh P, Kaderali L, Kalaghatgi P, Schlierf S . Accurate prediction of neuroblastoma outcome based on miRNA expression profiles. Int J Cancer. 2010; 127(10):2374-85. DOI: 10.1002/ijc.25436. View

14.

Asgharzadeh S, Pique-Regi R, Sposto R, Wang H, Yang Y, Shimada H . Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification. J Natl Cancer Inst. 2006; 98(17):1193-203. DOI: 10.1093/jnci/djj330. View

15.

Oberthuer A, Hero B, Berthold F, Juraeva D, Faldum A, Kahlert Y . Prognostic impact of gene expression-based classification for neuroblastoma. J Clin Oncol. 2010; 28(21):3506-15. DOI: 10.1200/JCO.2009.27.3367. View

16.

Vermeulen J, De Preter K, Lefever S, Nuytens J, De Vloed F, Derveaux S . Measurable impact of RNA quality on gene expression results from quantitative PCR. Nucleic Acids Res. 2011; 39(9):e63. PMC: 3089491. DOI: 10.1093/nar/gkr065. View

17.

Ohira M, Oba S, Nakamura Y, Isogai E, Kaneko S, Nakagawa A . Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas. Cancer Cell. 2005; 7(4):337-50. DOI: 10.1016/j.ccr.2005.03.019. View

18.

Wang W, Wilfred B, Baldwin D, Isett R, Ren N, Stromberg A . Focus on RNA isolation: obtaining RNA for microRNA (miRNA) expression profiling analyses of neural tissue. Biochim Biophys Acta. 2008; 1779(11):749-57. PMC: 2650220. DOI: 10.1016/j.bbagrm.2008.01.005. View

19.

Simon R . Roadmap for developing and validating therapeutically relevant genomic classifiers. J Clin Oncol. 2005; 23(29):7332-41. DOI: 10.1200/JCO.2005.02.8712. View

20.

Willems E, Leyns L, Vandesompele J . Standardization of real-time PCR gene expression data from independent biological replicates. Anal Biochem. 2008; 379(1):127-9. DOI: 10.1016/j.ab.2008.04.036. View