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

Abstract

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.

ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity

“…Additionally, the role of ACADL in NSCLC survival was evaluated using the online tool called: Kaplan-Meier plotter ( http://kmplot.com/analysis/ ), which incorporates mRNA‐seq and microarray profiles from different tumors, along with overall survival information collected from TCGA, Gene Expression Omnibus as well as Cancer Biomedical informatics Grid databases [ 31 ]. The protein expression of ACADL in LUAD, LUSC and normal lung tissues were investigated with The Human Pathology Atlas database ( https://www.proteinatlas.org ) which collects various proteins expression in major cancer and normal tissue types verified by immunohistochemistry (IHC) [ 32 ]. There is a total of 3 normal lung tissues, 10 LUSC samples, and 12 LUSC samples.…”

Superenhancers as master gene regulators and novel therapeutic targets in brain tumors

“…Roles of seRNAs in gliomas. Some seRNA-regulated immunerelated genes (IRGs) relevant in the tumor microenvironment were identified in glioma 154 , and they were used to construct a prognostic model that can predict the survival outcomes of patients with glioma. These glioma-specific seRNAs that regulate IRGs are located in adjacent sites and coexpressed in tumors, suggesting that they have potential as therapeutic targets 154,155 .…”

Emerging Role of Enhancer RNAs as Potential Diagnostic and Prognostic Biomarkers in Cancer

“…The result demonstrated how exact eRNAs and seRNAs were essential elements affecting survival outcomes. The obtained results might be considered to progress the therapeutic outcomes and extend the OS of glioma patients as well as other cancer types [ 110 ].…”