Construction and Verification of a Novel Pyroptosis-Related lncRNA Signature Associated with Immune Landscape in Gliomas

Abstract

Gliomas are the most common tumor in the central nervous system with limited prognostic markers making it difficult to research progression. Induction of cellular immunogenic death is a promising treatment for glioma. Pyroptosis is one of the recently discovered programmed immuogenic cell death modes which remains unclear in glioma. We obtained glioma datasets from the CGGA and TCGA websites. Pearson correlation analysis was used to find pyroptosis-related lncRNAs. Subsequently, the univariate, LASSO, and multivariate Cox regression were applied to construct a prognostic signature based on pyroptosis-related lncRNAs. Kaplan-Meier plots, ROC curves, and PCA were utilized for testing the prognostic performance of the signature. We conducted the univariate and multivariate Cox regressions to ascertain if the signature worked as an independent factor for predicting overall survival (OS) for individuals with glioma from other characteristics. For evaluating the immune landscape differences between the subgroups, ESTIMATE, CIBERTSORT, and ssGSEA were adopted. Additionally, biological functions and pathways of DEGs were identified by KEGG and GO. We also screened potential drugs and measured sensitivities of chemotherapeutics between the subgroups by CellMiner and pRRophetic package. Finally, shRNA was conducted to knockdown of COX10-AS1 in U87 cells to determine its relationship with pyroptosis. We successfully created an effective pyroptosis-related lncRNA signature that divided individuals into groups of low- and high-risk, and individuals in the high-risk group were with poor prognosis in comparison to the individuals in the other group. A nomogram including clinical factors and risk scores to predict the OS was built. Furthermore, the two groups appeared to have different immune landscapes; the high-risk group showed greater levels of ESTIMATE scores, immune cell infiltration, and immune checkpoints. Additionally, immune-related pathways and functions were shown to be enriched according to KEGG and GO findings. Knockdown of COX10-AS1 inhibited U87 cell growth, upregulated CASP1 and NLRP3, and released more IL1-β and IL-18 than the negative control. In summary, our study developed an lncRNA signature related to pyroptosis for OS prediction of gliomas and demonstrated its relationship with immune infiltration and drug sensitivity.