Article

miRNA expression profiling enables risk stratification in archived and fresh neuroblastoma tumor samples.

Center for Medical Genetics; Department of Paediatric Hematology and Oncology, Ghent University Hospital, Ghent, Belgium.
Clinical Cancer Research (Impact Factor: 7.84). 12/2011; 17(24):7684-92. DOI: 10.1158/1078-0432.CCR-11-0610
Source: PubMed

ABSTRACT 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.
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.
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.
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.

0 Bookmarks
 · 
357 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and displays remarkable heterogeneity in clinical behaviors, ranging from spontaneous regression to rapid progression or resistance to multimodal treatment. Recent evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are involved in tumor development and progression. This article aimed to review recent advances in investigating the roles of miRNAs in NB. We searched the PubMed/MEDLINE database for articles about the expression profile, functions and target genes of miRNAs in NB. We reviewed the most recent evidence regarding the functional roles of oncogenic and tumor suppressive miRNAs in NB and application of novel miRNA-based methods for diagnostic, prognostic and therapeutic purposes. Deregulation of miRNAs is associated with the development and progression of NB, suggesting that miRNAs may serve as novel targets for the treatment of high-risk NB patients. However, their precise functions and underlying mechanisms still warrant further studies.
    World Journal of Pediatrics 02/2014; 10(1):10-6. · 1.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastoma, a malignant embryonal tumor of the sympathetic nervous system, is the most common solid extracranial malignancy of childhood and accounts for 15 % of all childhood cancer deaths. The biological behavior of neuroblastoma is extensively heterogeneous, ranging from spontaneous regression to rapid progression despite multimodal aggressive therapy. Although the molecular basis of neuroblastoma has received considerable attention over the past decade, elucidating the mechanisms for the aggressive progression of neuroblastoma is needed for improving the efficacy of treatment. miRNAs (microRNAs) are small non-coding RNA molecules generally 19-22 nucleotides in length. miRNAs regulate 60 % of human gene expression at the post-transcriptional level by targeting regions of sequence complementarity on the 3'-untranslated regions (3'-UTRs) of specific mRNAs. miRNAs can either cause degradation of mRNAs or can inhibit their translation and therefore play major roles in normal growth and development. miRNA dysregulation has oncogenic or tumor-suppressive functions in virtually all forms of cancer, including neuroblastoma. The present review highlights the current insights on dysregulated miRNAs in neuroblastoma and on their roles in the diagnosis, prognosis, and treatment of this malignancy. As a rapidly evolving field of basic and biomedical sciences, miRNA research holds a great potential to impact on the management of neuroblastoma.
    Neurochemical Research 01/2014; · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pan-genomic analyses of genetic and epigenetic alterations and gene expression profiles are providing important new insights into the pathogenesis and molecular classification of cancers. The technologies and methods used for these studies are rapidly diversifying and improving. The use of such methodologies for the analysis of adrenocortical tumours has revealed clear transcriptomic (mRNA and microRNA expression profiles), epigenomic (DNA methylation profiles) and genomic (DNA mutations and chromosomal alterations) differences between benign and malignant tumours. Interestingly, genomic studies of adrenal cancers have also identified subtypes of malignant tumours, which demonstrate distinct patterns of molecular alterations and are associated with different clinical outcomes. These discoveries have created the opportunity for classifying adrenocortical tumours on the basis of molecular analyses. Following these genomic studies, efforts to develop new molecular tools that improve diagnosis and prognostication of patients with adrenocortical tumours have also been made. This Review describes the progress that has been made towards classification of adrenocortical tumours to date based on key genomic approaches. In addition, the potential for the development and use of various molecular tools to personalize the management of patients with adrenocortical tumours is discussed.
    Nature Reviews Endocrinology 02/2014; · 11.03 Impact Factor