Identification of a long noncoding RNA signature to predict outcomes of glioblastoma

Long noncoding RNAs (lncRNAs) are a novel class of gene regulators involved in tumor biogenesis. Glioblastoma is the most common and malignant type of brain tumor. The function and prognostic significance of lncRNAs in glioblastoma remain unclear. In the present study, updated gene annotations were adopted to investigate lncRNA expression profiles in publicly available glioma microarray datasets from the Gene Expression Omnibus and the Repository for Molecular Brain Neoplasia Data. In a training set of 108 samples of glioblastoma, using univariate Cox regression analysis with a permutation P<0.005, four lncRNAs, including insulin-like growth factor binding protein 7-antisense 1 (IGFBP7-AS1), were significantly associated with patient overall survival. These four lncRNAs were integrated as an expression-based molecular signature to divide patients in the training set into high-risk and low-risk subgroups, with distinct survival rates (hazard ratio, 2.72; 95% CI, 1.71–4.31; P<0.001). The prognostic value of the lncRNA signature was confirmed in two additional datasets comprising a total of 147 samples from patients with glioblastoma. The prognostic value of this signature was independent of age and Karnofsky performance status. This signature was also able to predict different outcomes in cases of glioblastoma associated with an isocitrate dehydrogenase 1 mutation. Further bioinformatics analyses revealed that ‘epithelial-mesenchymal transition’ and ‘p53 pathway’ gene sets were enriched in glioblastoma samples with higher IGFBP7-AS1 expression. Furthermore, in vitro experiments demonstrated that knockdown of IGFBP7-AS1 inhibited the viability, migration and invasion of U87 and U251 glioma cells. In conclusion, the present study identified a lncRNA signature able to predict glioblastoma outcomes, and provided novel information regarding the role of IGFBP7-AS1 in glioma development.