Prospective Series of Nine Long Noncoding RNAs Associated with Survival of Patients with Glioblastoma

Abstract

Objective To analyze the long noncoding RNA (lncRNA) expression profile of glioblastoma multiforme (GBM) and identify prognosis-related lncRNAs, as well as their related protein-coding genes and functions.

Method The lncRNA expression profiles were obtained by microarray in six samples each of GBM and normal brain tissue. The lncRNAs expressed were significantly different between the two groups and used to detect their associations with patient survival time by downloading the related data from The Cancer Genome Atlas (TCGA). The total RNA-sequencing data of 152 patients diagnosed GBM level 3 with complete clinic information was downloaded. The survival time–dependent lncRNAs were identified by multivariate Cox regression analysis. For the survival time–dependent lncRNAs, we used the Pearson correlation coefficient and z test to search their associated protein-coding genes downloaded from TCGA. Functions of these genes were annotated by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results More than 1,000 antisense lncRNAs and enhancer lncRNAs were selected for analysis in this study. Data from 152 cases with RNA-seq of GBM level 3 with complete information on GBM were downloaded from the TCGA database. Univariate Cox regression analysis revealed 19 lncRNAs with survival time dependency. These nine lncRNAs were used to construct our survival model via multivariate Cox regression analysis: TP73-AS1, AC078883.3, RP11–944L7.4, HAR1B, RP4–635E18.7, HOTAIR, SAPCD1-AS1, AC104653.1, and RP5–1172N10.2. The nine lncRNAs associated with them were inputted into the DAVID database for gene ontology and KEGG function enrichment analysis. The result showed these genes were enriched with ion binding, transport, cell-cell signaling, plasma membrane parts, and more, and they were mainly related to neuroactive ligand-receptor interaction pathway, calcium signaling pathway, and the mitogen-activated protein kinase signaling pathway.

Conclusion The nine lncRNAs were a set of biomarkers for the prognosis of patients with GBM, enabling a more accurate prediction of survival and revealing more biological functions.

Keywords

noncoding linking RNAs - survival time - glioblastoma

• References

• 1 Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol 2005; 109 (01) 93-108
• 2 Ray S, Bonafede MM, Mohile NA. Treatment patterns, survival, and healthcare costs of patients with malignant gliomas in a large US commercially insured population. Am Health Drug Benefits 2014; 7 (03) 140-149
• 3 Jiang T, Mao Y, Ma W. , et al; Chinese Glioma Cooperative Group (CGCG). CGCG clinical practice guidelines for the management of adult diffuse gliomas. Cancer Lett 2016; 375 (02) 263-273
• 4 Wang Q, Zhang J, Liu Y. , et al. A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. Cancer Lett 2016; 373 (02) 251-259
• 5 Cui Y, Yi L, Zhang MM. , et al. Withdrawn: Knockdown of LncRNA HOXA11 antisense promotes glioma cell apoptosis via sponging MiR-140-5p. Oncol Res 2017
• 6 Liao Y, Shen L, Zhao H. , et al. LncRNA CASC2 interacts with miR-181a to modulate glioma growth and resistance to TMZ through PTEN pathway. J Cell Biochem 2017; 118 (07) 1889-1899
• 7 Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol 2013; 26 (02) 155-165
• 8 Zhang T, Wang YR, Zeng F, Cao HY, Zhou HD, Wang YJ. LncRNA H19 is overexpressed in glioma tissue, is negatively associated with patient survival, and promotes tumor growth through its derivative miR-675. Eur Rev Med Pharmacol Sci 2016; 20 (23) 4891-4897
• 9 He Z, Wang Y, Huang G, Wang Q, Zhao D, Chen L. The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP. Arch Biochem Biophys 2017; ;623-624: 1-8
• 10 Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10 (03) 155-159
• 11 Zhou X, Ren Y, Zhang J. , et al. HOTAIR is a therapeutic target in glioblastoma. J Oncotarget 2015; 6 (10) 8353-8365
• 12 Zhang R, Jin H, Lou F. The long non-coding RNA TP73–AS1 interacted with miR-142 to modulate brain glioma growth through HMGB1/RAGE pathway. J Cell Biochem 2018; 119 (04) 3007-3016
• 13 Sun J, Cheng L, Shi H. , et al. A potential panel of six-long non-coding RNA signature to improve survival prediction of diffuse large-B-cell lymphoma. J Sci Rep 2016; 6: 27842