An Immune-Related Six-lncRNA Signature to Improve Prognosis Prediction of Glioblastoma Multiforme

Abstract

Recent studies have demonstrated the utility and superiority of long non-coding RNAs (lncRNAs) as novel biomarkers for cancer diagnosis, prognosis, and therapy. In the present study, the prognostic value of lncRNAs in glioblastoma multiforme was systematically investigated by performing a genome-wide analysis of lncRNA expression profiles in 419 glioblastoma patients from The Cancer Genome Atlas (TCGA) project. Using survival analysis and Cox regression model, we identified a set of six lncRNAs (AC005013.5, UBE2R2-AS1, ENTPD1-AS1, RP11-89C21.2, AC073115.6, and XLOC_004803) demonstrating an ability to stratify patients into high- and low-risk groups with significantly different survival (median 0.899 vs. 1.611 years, p = 3.87e-09, log-rank test) in the training cohort. The six-lncRNA signature was successfully validated on independent test cohort of 219 patients with glioblastoma, and it revealed superior performance for risk stratification with respect to existing lncRNA-related signatures. Multivariate Cox and stratification analysis indicated that the six-lncRNA signature was an independent prognostic factor after adjusting for other clinical covariates. Further in silico functional analysis suggested that the six-lncRNA signature may be involved in the immune-related biological processes and pathways which are very well known in the context of glioblastoma tumorigenesis. The identified lncRNA signature had important clinical implication for improving outcome prediction and guiding the tailored therapy for glioblastoma patients with further prospective validation.

LncRNA SNHG16 drives proliferation, migration, and invasion of hemangioma endothelial cell through modulation of miR‐520d‐3p/STAT3 axis

“…[22][23][24][25] As diagnostic or prognostic markers, ceRNAs have been uncovered in many reports. [26][27][28][29][30][31][32] In some cases, lncRNAs can participate in ceRNA pattern to modulate gene expression. 33,34 In this study, we supposed that SNHG16 might be a ceRNA in HemECs.…”

A prognostic signature for lower-grade gliomas based on expression of long noncoding RNAs

“…However, the sequence of one of the lncRNAs in Chen et al, 2017, CR613436, was removed by the submitter on NCBI. Recently, the role of immune-related genes in glioma malignancies is gaining attention leading to the discovery of immune-related lncRNA-based prognostic markers for GBMs and anaplastic gliomas [40, 41]. Remarkably, there is no overlap between the prognostic lncRNAs identified in the aforementioned studies.…”

“…The level of NF-κB increases as the tumors progress in astrocytic tumors [42, 43] and STAT3 is constitutively active in GBMs [44, 45]. Immune related pathways are also known to be involved in glioma tumor cell proliferation [46], survival [40], invasion [47] and chemoresistance [48]. In addition, epithelial-mesenchymal transition (associated with invasion) and active cell proliferation are suppressed if UVA8 lncRNAs are high, and this leads to better outcome, consistent with our understanding of how invasion and cell proliferation negatively impact outcome.…”

Identification of a multidimensional transcriptome prognostic signature for lung adenocarcinoma

“…Protein-coding genes (PCGs) are the most common biomarkers and involved in the many key biological processes which can be powerful predictors of survival in patients in different cancers. For instance, a 3-lncRNA signature can be a new biomarker for the esophageal squamous cell carcinoma prognosis, 18 an immune-related 6-lncRNA signature could improve prognosis prediction of glioblastoma multiforme 19 and a potential signature of eight long non-coding RNAs could predict survival in patients with non-small cell lung cancer. Long non-coding RNA (lncRNA) becomes new participant in tumorigenesis due to their various functions in a variety of cancer gene regulatory mechanisms, and has important clinical implications in terms of prognosis.…”

“…[7][8][9][10][11][12][13][14] Recent studies have constructed many lncRNA signature [15][16][17] to predict the prognosis of patients. For instance, a 3-lncRNA signature can be a new biomarker for the esophageal squamous cell carcinoma prognosis, 18 an immune-related 6-lncRNA signature could improve prognosis prediction of glioblastoma multiforme 19 and a potential signature of eight long non-coding RNAs could predict survival in patients with non-small cell lung cancer. 20 The advantage of combining PCGs with lncRNAs as prognostic markers is to show the disorder alteration of patients with cancer in greater detail from multiple dimensions.…”