Clinical Significance and Immune Landscape of a Pyroptosis-Derived LncRNA Signature for Glioblastoma

Zhe Xing; Zaoqu Liu; Xudong Fu; Shaolong Zhou; Long Liu; Qin Dang; Chunguang Guo; Xiaoyong Ge; Taoyuan Lu; Youyang Zheng; Lirui Dai; Xinwei Han; Xinjun Wang

doi:10.3389/fcell.2022.805291

Clinical Significance and Immune Landscape of a Pyroptosis-Derived LncRNA Signature for Glioblastoma

Front Cell Dev Biol. 2022 Feb 10:10:805291. doi: 10.3389/fcell.2022.805291. eCollection 2022.

Authors

Zhe Xing^{1

2}, Zaoqu Liu³, Xudong Fu^{1

2}, Shaolong Zhou^{1

2}, Long Liu⁴, Qin Dang⁵, Chunguang Guo⁶, Xiaoyong Ge³, Taoyuan Lu⁷, Youyang Zheng⁸, Lirui Dai^{1

2}, Xinwei Han³, Xinjun Wang^{1

2}

Affiliations

¹ Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Henan International Joint Laboratory of Glioma Metabolism and Microenvironment Research, Zhengzhou, China.
³ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁴ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁵ Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁶ Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁷ Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Zhengzhou, China.
⁸ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Introduction: Pyroptosis was recently implicated in the initiation and progression of tumors, including glioblastoma (GBM). This study aimed to explore the clinical significance of pyroptosis-related lncRNAs (PRLs) in GBM. Methods: Three independent cohorts were retrieved from the TCGA and CGGA databases. The consensus clustering and weighted gene coexpression network analysis (WGCNA) were applied to identify PRLs. The LASSO algorithm was employed to develop and validate a pyroptosis-related lncRNA signature (PRLS) in three independent cohorts. The molecular characteristics, clinical significances, tumor microenvironment, immune checkpoints profiles, and benefits of chemotherapy and immunotherapy regarding to PRLS were also explored. Results: In the WGCNA framework, a key module that highly correlated with pyroptosis was extracted for identifying PRLs. Univariate Cox analysis further revealed the associations between PRLs and overall survival. Based on the expression profiles of PRLs, the PRLS was initially developed in TCGA cohort (n = 143) and then validated in two CGGA cohorts (n = 374). Multivariate Cox analysis demonstrated that our PRLS model was an independent risk factor. More importantly, this signature displayed a stable and accurate performance in predicting prognosis at 1, 3, and 5 years, with all AUCs above 0.7. The decision curve analysis also indicated that our signature had promising clinical application. In addition, patients with high PRLS score suggested a more abundant immune infiltration, higher expression of immune checkpoint genes, and better response to immunotherapy but worse to chemotherapy. Conclusion: A novel pyroptosis-related lncRNA signature with a robust performance was constructed and validated in multiple cohorts. This signature provided new perspectives for clinical management and precise treatments of GBM.

Keywords: chemotherapy; glioblastoma (GBM); immune landscape; immunotherapy; long non-coding RNA; prognostic signature; pyroptosis.