Diagnostic and Prognostic Potentials of Long Noncoding RNA ELF3-AS1 in Glioma Patients

Abstract

Objective: Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a crucial role in predicting survival for glioma patients. However, the potential function of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) in tumors remained largely unclear. The aim of this study was to explore the expression of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) and evaluate its functions in glioma patients. Patients and Methods. ELF3-AS1 expressions were examined by RT-PCR in 182 pairs of glioma specimens and adjacent normal tissues. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of ELF3-AS1. The chi-square tests were used to examine the associations between ELF3-AS1 expression and the clinicopathological characters. The overall survival (OS) and disease-free survival (DFS) were analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. The prognostic value of the ELF3-AS1 expression in glioma patients was further analyzed using univariate and multivariate Cox regression analyses. Loss-of-function assays were performed to determine the potential function of ELF3-AS1 on the proliferation and invasion of glioma cells.

Results: The ELF3-AS1 expression level was significantly higher in glioma specimens compared with adjacent nontumor specimens (p < 0.01). A high expression of ELF3-AS1 was shown to be associated with the WHO grade (p = 0.023) and KPS score (p = 0.012). ROC assays revealed that high ELF3-AS1 expression had an AUC value of 0.8073 (95% CI: 0.7610 to 0.8535) for glioma. Using the Kaplan-Meier analysis, we found that patients with a high ELF3-AS1 expression had significantly poor OS (p = 0.006) and DFS (p = 0.0002). In a multivariate Cox model, we confirmed that ELF3-AS1 expression was an independent poor prognostic factor for glioma patients. The functional assay revealed that knockdown of ELF3-AS1 suppressed the proliferation and invasion of glioma cells.

Conclusions: Our findings confirmed that ELF3-AS1 functions as an oncogene in glioma and indicated that ELF3-AS1 is not only an important prognostic marker but also a potential therapy target for glioma.

Figure 1

The expression of ELF3-AS1 and its diagnostic significance in glioma. (a) The expression levels of ELF3-AS1 in glioma tissues were significantly higher than those in corresponding noncancerous tissues. (b) RT-PCR for the determination of ELF3-AS1 expression in the glioma specimens with different stages. (c) qRT-PCR analysis of the expression of ELF3-AS1 in glioma cell lines and NHA cells. (d) ROC curve for diagnostic value of ELF3-AS1 in glioma. ^∗∗p < 0.01, ^∗p < 0.05.

Figure 2

Kaplan-Meier curves estimating the 5-year overall survival rates according to the expression of ELF3-AS1 in patients with glioma.

Figure 3

Kaplan-Meier curves estimating the 5-year disease-free survival rates according to the expression of ELF3-AS1 in patients with glioma.

Figure 4

Effect of ELF3-AS1 on proliferation rate, colony formation ability, and invasion ability. (a) RT-PCR analysis of ELF3-AS1 knockdown efficiency in H4 and LN229 cells. (b, c) Cell proliferation was evaluated by CCK-8 assay in H4 and LN229 cells. (d) Colony-forming assays were performed to determine the growth of glioma cells. (e) Invasion ability was tested in Matrigel-coated transwell invasion chambers. ^∗∗p < 0.01, ^∗p < 0.05.