A necroptosis-related lncRNA signature was identified to predict the prognosis and immune microenvironment of IDH-wild-type GBM.

Introduction: Necroptosis-related genes are essential for the advancement of IDH-wild-type GBM. However, the putative effects of necroptosis-related lncRNAs (nrlncRNAs) in IDH-wild-type GBM remain unknown.

Methods: By using the TCGA and GTEx databases, a nrlncRNA prognostic signature was created using LASSO Cox regression. The median risk score was used to categorize the patients into low and high-risk groups. To confirm the validity, univariate, multivariate Cox regression and ROC curves were used. Furthermore, by enrichment analysis, immune correlation analysis, and drug sensitivity analysis, the targeted lncRNAs were selected for further verification. As the highest upregulated expression in tumor than peritumor specimens, RP11-131L12.4 was selected for phenotype and functional experiments in primary GBM cells.

Results: Six lncRNAs were proved to be closely related to necroptosis in IDH-1-wild-type GBM, which were used to create a new signature. For 1-, 2-, and 3-year OS, the AUCs were 0.709, 0.645 and 0.694, respectively. Patients in the low-risk group had a better prognosis, stronger immune function activity, and more immune cell infiltration. In contrast, enrichment analysis revealed that the malignant phenotype was more prevalent in the high-risk group. In vitro experiments indicated that RP11-131L12.4 increased the tumor proliferation, migration and invasion, but decreased the necroptosis. Moreover, this nrlncRNA was also proved to be negatively associated with patient prognosis.

Conclusion: The signature of nrlncRNAs may aid in the formulation of tailored and precise treatment for individuals with IDH-wild-type GBM. RP11-131L12.4 may play indispensable role in necroptosis suppression.