A novel signature of cuproptosis-related lncRNAs predicts prognosis in glioma: Evidence from bioinformatic analysis and experiments

Abstract

Background: Glioma patients often experience unfavorable outcomes and elevated mortality rates. Our study established a prognostic signature utilizing cuproptosis-associated long non-coding RNAs (CRLs) and identified novel prognostic biomarkers and therapeutic targets for glioma. Methods: The expression profiles and related data of glioma patients were obtained from The Cancer Genome Atlas, an accessible online database. We then constructed a prognostic signature using CRLs and evaluated the prognosis of glioma patients by means of Kaplan-Meier survival curves and receiver operating characteristic curves. A nomogram based on clinical features was employed to predict the individual survival probability of glioma patients. Functional enrichment analysis was conducted to identify crucial CRL-related enriched biological pathways. The role of LEF1-AS1 in glioma was validated in two glioma cell lines (T98 and U251). Results: We developed and validated a prognostic model for glioma with 9 CRLs. Patients with low-risk had a considerably longer overall survival (OS). The prognostic CRL signature may serve independently as an indicator of prognosis for glioma patients. In addition, functional enrichment analysis revealed significant enrichment of multiple immunological pathways. Notable differences were observed between the two risk groups in terms of immune cell infiltration, function, and immune checkpoints. We further identified four drugs based on their different IC50 values from the two risk groups. Subsequently, we discovered two molecular subtypes of glioma (cluster one and cluster two), with the cluster one subtype exhibiting a remarkably longer OS compared to the cluster two subtype. Finally, we observed that inhibition of LEF1-AS1 curbed the proliferation, migration, and invasion of glioma cells. Conclusion: The CRL signatures were confirmed as a reliable prognostic and therapy response indicator for glioma patients. Inhibition of LEF1-AS1 effectively suppressed the growth, migration, and invasion of gliomas; therefore, LEF1-AS1 presents itself as a promising prognostic biomarker and potential therapeutic target for glioma.

Keywords: LEF1-AS1; cuproptosis; glioma; immune infiltration; long non-coding RNA; prognostic signature; therapeutic response prediction.