A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Wei Tian¹  Qiuju Zhang¹  Guangcan Yan¹  Meina Liu¹  Xinhao Han¹  Kegong Chen²  Yanlong Liu³ 

[1] Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin, China;Department of Cardio-Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China;Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China;

关键词: enhancer RNA;    super enhancer RNA;    immune-related gene;    prognosis;    glomas;   

DOI  :  10.3389/fcell.2021.798445

 received in 2021-10-20, accepted in 2021-12-30,  发布年份 2022

来源: Frontiers

【 摘 要 】

Background: Gliomas are the most malignant tumors of the nervous system. Even though their survival outcome is closely affected by immune-related genes (IRGs) in the tumor microenvironment (TME), the corresponding regulatory mechanism remains poorly characterized.Methods: Specific enhancer RNAs (eRNAs) can be found in tumors, where they control downstream genes. The present study aimed to identify eRNA-regulated IRGs, evaluate their influence on the TME, and use them to construct a novel prognostic model for gliomas.Results: Thirteen target genes (ADCYAP1R1, BMP2, BMPR1A, CD4, DDX17, ELN, FGF13, MAPT, PDIA2, PSMB8, PTPN6, SEMA6C, and SSTR5) were identified and integrated into a comprehensive risk signature, which distinguished two risk subclasses. Discrepancies between these subclasses were compared to explore potential mechanisms attributed to eRNA-regulated genes, including immune cell infiltration, clinicopathological features, survival outcomes, and chemotherapeutic drug sensitivity. Furthermore, the risk signature was used to construct a prognostic tool that was evaluated by calibration curve, clinical utility, Harrell’s concordance index (0.87; 95% CI: 0.84–0.90), and time-dependent receiver operator characteristic curves (AUCs: 0.93 and 0.89 at 3 and 5 years, respectively). The strong reliability and robustness of the established prognostic tool were validated in another independent cohort. Finally, potential subtypes were explored in patients with grade III tumors.Conclusion: Overall, eRNAs were associated with immune-related dysfunctions in the TME. Targeting of IRGs regulated by eRNAs could improve immunotherapeutic/therapeutic outcomes.

【 授权许可】

Unknown   
Copyright © 2022 Tian, Chen, Yan, Han, Liu, Zhang and Liu.