Long non-coding RNA expression profiles predict clinical phenotypes in glioma

Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
Neurobiology of Disease (Impact Factor: 5.08). 06/2012; 48(1):1-8. DOI: 10.1016/j.nbd.2012.06.004
Source: PubMed


Glioma is the commonest form of primary brain tumor in adults with varying malignancy grades and histological subtypes. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been shown to play important roles in cancer development. To discover novel tumor-related lncRNAs and determine their associations with glioma subtypes, we first applied a lncRNA classification pipeline to identify 1970 lncRNAs that were represented on Affymetrix HG-U133 Plus 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published glioma gene expression profiles of 268 clinical specimens, and identified sets of lncRNAs that were unique to different histological subtypes (astrocytic versus oligodendroglial tumors) and malignancy grades. These lncRNAs signatures were then subject to validation in another non-overlapping, independent data set that contained 157 glioma samples. This is the first reported study that correlates lncRNA expression profiles with malignancy grade and histological differentiation in human gliomas. Our findings indicate the potential roles of lncRNAs in the biogenesis, development and differentiation of gliomas, and provide an important platform for future studies.

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    • "First of all, the probable mechanism of action of lncRNAs has not been delineated due to its heterogeneity [42]. Secondly, although Affymetrix HG-U133 Plus 2.0 array series is one of the most commonly used commercial microarrays in human cancer proļ€filing, it does not represent all of the possible lncRNAs presented [18]. Thirdly, the sample size of each dataset is relatively small, which may reduce the accuracy of the results. "
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    • "CRNDE was originally discovered as an upregulated gene in colorectal adenomas and cancers, whereas it shows little to no expression in normal colon epithelium [1]. In addition to CRC, CRNDE overexpression has been observed in many other cancers, including gliomas in which it is the most upregulated lncRNA [2] [3]. CRNDE is a long non-coding RNA (lncRNA), defined as a class of non-protein coding transcripts over 200 nucleotides long; there is now abundant evidence for lncRNA roles in critical cellular processes, especially transcriptional and epigenetic regulation . "
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    • "data to profile lncRNA expression across different types and grades of human gliomas. Of the 129 lncRNAs identified as differentially expressed in gliomas, the results consistently and convincingly identified CRNDE (both probesets) as the most highly upregulated lncRNA (32-fold; Zhang et al., 2012). This was the case for low and high grade astrocytomas (15-and 36-fold, respectively ) and oligodendrogliomas (8-and 29-fold, respectively), and CRNDE levels correlated positively with tumor grade in both types. "
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