Expression and Clinical Significance of Long Non-Coding RNA RP4-669H2.1 in Glioblastoma

Abstract

Neuroglioma is the most common malignant tumor in the central nervous system and still has a poor prognosis. Here, we investigated the prognostic value of long non-coding RNAs(lncRNAs) in glioblastoma. We first analyzed the lncRNA expression profiles of glioblastoma (GBM) in The Cancer Genome Atlas database and selected the most differential survival genes (lncRNA RP4-669H2.1) for further validation. We then performed qRT-PCR using samples of 88 glioblastoma patients treated in our department between January 2011 and December 2017 that were retrospectively selected to validate the prognostic value of RP4-669H2.1expression in glioblastoma. Using a Cox multivariate analysis, we explored the prognostic value of RP4-669H2.1 and analyzed whether it was an independent prognostic factor. This analysis confirmed that the RP4-669H2.1 expression was significantly associated with glioblastoma-associated mortality in this patient cohort (P =1.80E–05) in TCGA database. In fact, the overall survival (OS) of the RP4-669H2.1 high-expression group (78 cases) was lower than that of the low-expression group (49 cases) (P = 4.6E–06) in TCGA database. Moreover, the TNM stage of the RP4-669H2.1 high-expression group was higher than that of the RP4-669H2.1 low-expression group (P = 0.001). A multivariate analysis further showed that a higher TNM stage (OR = 2.167, 95% CI: 1.349–3.479) and a higher RP4-669H2.1 expression (OR = 2.933, 95% CI: 1.122–7.663) were independent risk factors for the OS of glioblastoma patients. Finally, we predicted the target genes of RP4-669H2.1 using a Multi Experiment Matrix and annotated their biological functions. We observed that the target genes of RP4-669H2.1 were mainly enriched in biological functions related to DNA-binding transcription factor activity. Among these, we selected SMAD6 because the expression of RP4-669H2.1 was positively correlated with that of SMAD6 in glioblastoma. Overall, we conclude that the upregulation of RP4-669H2.1 is an independent poor prognosis factor for glioblastoma and that it can regulate the DNA-binding activity of transcription factors.