Identification of Necroptosis-related Molecular Subtypes and Construction of Necroptosis-related Gene Signature for Glioblastoma Multiforme

Zhiyong Li; Yinghui Jin; Tianshi Que; Xi-An Zhang; Guozhong Yi; Haojie Zheng; Xi Yuan; Xiaoyan Wang; Haiyan Xu; Jing Nan; Chao Chen; Yuankui Wu; Guanglong Huang

doi:10.2174/0929867331666230804104329

Identification of Necroptosis-related Molecular Subtypes and Construction of Necroptosis-related Gene Signature for Glioblastoma Multiforme

Curr Med Chem. 2023 Aug 4. doi: 10.2174/0929867331666230804104329. Online ahead of print.

Authors

Zhiyong Li^{1

2}, Yinghui Jin³, Tianshi Que^{1

2}, Xi-An Zhang¹, Guozhong Yi¹, Haojie Zheng¹, Xi Yuan¹, Xiaoyan Wang^{1

2

2}, Haiyan Xu^{1

2}, Jing Nan^{1

2}, Chao Chen^{1

2}, Yuankui Wu⁴, Guanglong Huang^{1

2}

Affiliations

¹ Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
² Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
³ Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
⁴ Department of Medical Imaging, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

PMID: 37539935
DOI: 10.2174/0929867331666230804104329

Abstract

Background Necroptosis is a highly regulated and genetically controlled process, and therefore, attention has been paid to the exact effects of this disorder on a variety of diseases, including cancer. An in-depth understanding of the key regulatory factors and molecular events that trigger necroptosis can not only identify patients at risk of cancer development but can also help to develop new treatment strategies. Aims This study aimed to increase understanding of the complex role of necroptosis in glioblastoma multiforme (GBM) and provide a new perspective and reference for accurate prediction of clinical outcomes and gene-targeted therapy in patients with GBM. The objective of this study was to analyze the gene expression profile of necroptosis regulatory factors in glioblastoma multiforme (GBM) and establish a necroptosis regulatory factor-based GBM classification and prognostic gene signature to recognize the multifaceted impact of necroptosis on GBM. Method The necroptosis score of the glioblastoma multiforme (GBM) sample in TCGA was calculated by ssGSEA, and the correlation between each gene and the necroptosis score was calculated. Based on necroptosis score-related genes, unsupervised consensus clustering was employed to classify patients. The prognosis, tumor microenvironment (TME), genomic changes, biological signal pathways and gene expression differences among clusters were analyzed. The gene signature of GBM was constructed by Cox and LASSO regression analysis of differentially expressed genes (DEGs). Result Based on 34 necroptosis score-related genes, GBM was divided into two clusters with different overall survival (OS) and TME. A necroptosis-related gene signature (NRGS) containing 8 genes was developed, which could stratify the risk of GBM in both the training set and verification set and had good prognostic value. NRGS and age were both independent prognostic indicators of GBM, and a nomogram developed by the integration of both of them showed a better predictive effect than traditional clinical features. Conclusion In this study, patients from public data sets were divided into two clusters and the unique TME and molecular characteristics of each cluster were described. Furthermore, an NRGS was constructed to effectively and independently predict the survival outcome of GBM, which provides some insights for the implementation of personalized precision medicine in clinical practice.

Keywords: Glioblastoma multiforme; Necroptosis; molecular clusters; mutation; prognosis; tumor microenvironment.