Image9_A Novel Prognostic Tool for Glioma Based on Enhancer RNA-Regulated Immune Genes.PDF
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.
History
References
- https://doi.org//10.5498/wjp.v10.i9.212
- https://doi.org//10.1186/s13059-017-1349-1
- https://doi.org//10.1038/nature08460
- https://doi.org//10.1186/s40478-019-0704-8
- https://doi.org//10.3390/ijms21196999
- https://doi.org//10.1007/s00401-018-1913-0
- https://doi.org//10.3389/fonc.2021.672928
- https://doi.org//10.1186/s13073-017-0424-2
- https://doi.org//10.1212/WNL.0000000000002770
- https://doi.org//10.3390/ijms22094899
- https://doi.org//10.18632/oncotarget.21586
- https://doi.org//10.1093/jnen/nlaa059
- https://doi.org//10.1371/journal.pone.0107468
- https://doi.org//10.1007/s00401-015-1427-y
- https://doi.org//10.1038/nn.4185
- https://doi.org//10.1016/j.ajpath.2020.12.006
- https://doi.org//10.1021/acsami.1c04164
- https://doi.org//10.1073/pnas.1324151111
- https://doi.org//10.1080/21691401.2018.1549062
- https://doi.org//10.1093/neuonc/nox125
- https://doi.org//10.1093/biostatistics/kxj037
- https://doi.org//10.1155/2015/541984
- https://doi.org//10.18632/oncotarget.7411
- https://doi.org//10.1126/science.aan6733
- https://doi.org//10.1080/15476286.2020.1712895
- https://doi.org//10.1158/0008-5472.CAN-17-0307
- https://doi.org//10.1073/pnas.1616697113
- https://doi.org//10.1038/s41598-017-05688-0
- https://doi.org//10.3390/cells10061275
- https://doi.org//10.1186/s12943-020-01253-y
- https://doi.org//10.1038/nature14432
- https://doi.org//10.3389/fimmu.2018.02924
- https://doi.org//10.1093/bib/bbab260
- https://doi.org//10.2147/CMAR.S171855
- https://doi.org//10.1182/blood-2014-10-604777
- https://doi.org//10.1158/0008-5472.CAN-18-0367
- https://doi.org//10.1038/ng.3167
- https://doi.org//10.1007/s11060-017-2704-5
- https://doi.org//10.7150/thno.17886
- https://doi.org//10.1001/jamaoncol.2020.1024
- https://doi.org//10.1016/j.molcel.2014.08.023
- https://doi.org//10.1016/j.pharmthera.2019.02.014
- https://doi.org//10.1016/j.ccell.2017.06.003
- https://doi.org//10.3389/fgene.2020.612037
- https://doi.org//10.1111/cpr.12988
- https://doi.org//10.1016/j.intimp.2021.108376
- https://doi.org//10.1016/s0378-1119%2803%2900400-1
- https://doi.org//10.1186/s12883-020-01640-4
- https://doi.org//10.1016/j.cels.2018.01.013
- https://doi.org//10.1158/1078-0432.CCR-16-2598
- https://doi.org//10.1038/s41467-019-12543-5
- https://doi.org//10.1038/s41591-019-0449-8
- https://doi.org//10.1038/s41591-019-0349-y
- https://doi.org//10.1186/s13578-020-00396-1
CC BY 4.0