Identification of Ferroptosis-Related Biomarkers for Prognosis and Immunotherapy in Patients With Glioma

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Feb 17

PMID 35174152

Authors

Junfeng Shi

Donglin Lai

Xiaojia Zuo

Dingsheng Liu

Bing Chen

Yanjun Zheng

Changlian Lu

Xuefeng Gu

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is a novel type of iron- and ROS-dependent cell death and is involved in various diseases. LncRNAs are involved and play important roles in the occurrence and development of several cancers. However, researches about the role of ferroptosis-related lncRNAs in glioma are relatively rare. Here, we identified nine ferroptosis-related lncRNAs and then constructed a prognostic model by the LASSO and Cox analysis. The model could predict overall survival with high sensitivity and specificity according to ROC curves. In addition, the cell cycle, p53 signaling, apoptosis, and oxidative phosphorylation pathways were obviously enriched in the pathogenesis of glioma by gene set enrichment analysis. A nomogram was constructed by integrating several independent prognostic clinicopathological features, and it could provide a valuable predictive tool for overall survival. Furthermore, a strong correlation between these nine lncRNAs and immunotherapy was found. Glioma patients in the high-risk group had higher TMB using somatic mutation data, different immune infiltration, and higher expression of immune checkpoints, indicating these patients might benefit from immune checkpoint inhibitor therapy. In summary, these nine ferroptosis-related lncRNAs were promising biomarkers for predicting overall survival and guiding immunotherapy or future immune checkpoint inhibitor development for glioma patients.

Citing Articles

Prognostic modeling of disulfidptosis gene-associated lncRNAs aids in identifying the tumor microenvironment and guiding the selection of therapy.

Jiang Y, Huang X, Huang R, Deng K, Dai L, Wang B Discov Oncol. 2025; 16(1):273.

PMID: 40053203 PMC: 11889292. DOI: 10.1007/s12672-025-02033-0.

Abnormal Histopathological Expression of Klotho, Ferroptosis, and Circadian Clock Regulators in Pancreatic Ductal Adenocarcinoma: Prognostic Implications and Correlation Analyses.

Garcia-Montero C, Fraile-Martinez O, Cobo-Prieto D, De Leon-Oliva D, Boaru D, De Castro-Martinez P Biomolecules. 2024; 14(8).

PMID: 39199335 PMC: 11353028. DOI: 10.3390/biom14080947.

Machine learning unveils immune-related signature in multicenter glioma studies.

Yang S, Wang X, Huan R, Deng M, Kong Z, Xiong Y iScience. 2024; 27(4):109317.

PMID: 38500821 PMC: 10946333. DOI: 10.1016/j.isci.2024.109317.

Deeper insight into ferroptosis: association with Alzheimer's, Parkinson's disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis.

Yadav V, Choudhary N, Gacem A, Verma R, Hasan M, Imam M Redox Rep. 2023; 28(1):2269331.

PMID: 38010378 PMC: 11001282. DOI: 10.1080/13510002.2023.2269331.

Single-Cell Sequencing Reveals Necroptosis-Related Prognostic Genes of Glioblastoma.

Zheng P, Ren D, Cong Y, Zhang X, Zhang Y Oxid Med Cell Longev. 2023; 2023:2926655.

PMID: 36860730 PMC: 9970716. DOI: 10.1155/2023/2926655.

References

Zhuang C, Liu Y, Fu S, Yuan C, Luo J, Huang X . Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling. Front Mol Biosci. 2020; 7:616768. PMC: 7755977. DOI: 10.3389/fmolb.2020.616768. View

Powles T, Park S, Voog E, Caserta C, Valderrama B, Gurney H . Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020; 383(13):1218-1230. DOI: 10.1056/NEJMoa2002788. View

Shi Y, Lim S, Liang Q, Iyer S, Wang H, Wang Z . Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma. Nature. 2019; 567(7748):341-346. PMC: 6655586. DOI: 10.1038/s41586-019-0993-x. View

Chen L, Li X, Liu L, Yu B, Xue Y, Liu Y . Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and cystathionine-γ-lyase function. Oncol Rep. 2015; 33(3):1465-74. DOI: 10.3892/or.2015.3712. View

Zhang X, Zhuang J, Liu L, He Z, Liu C, Ma X . Integrative transcriptome data mining for identification of core lncRNAs in breast cancer. PeerJ. 2019; 7:e7821. PMC: 6786248. DOI: 10.7717/peerj.7821. View

Gu X, Wan G, Chen N, Li J, Chen B, Tang Y . DGKζ Plays Crucial Roles in the Proliferation and Tumorigenicity of Human glioblastoma. Int J Biol Sci. 2019; 15(9):1872-1881. PMC: 6743304. DOI: 10.7150/ijbs.35193. View

Wang T, Li X, Sun S . EX527, a Sirt-1 inhibitor, induces apoptosis in glioma via activating the p53 signaling pathway. Anticancer Drugs. 2019; 31(1):19-26. DOI: 10.1097/CAD.0000000000000824. View

OHara M, OReilly E, Varadhachary G, Wolff R, Wainberg Z, Ko A . CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 2021; 22(1):118-131. DOI: 10.1016/S1470-2045(20)30532-5. View

Baas P, Scherpereel A, Nowak A, Fujimoto N, Peters S, Tsao A . First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021; 397(10272):375-386. DOI: 10.1016/S0140-6736(20)32714-8. View

10.

Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D . CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 2020; 19(1):43. PMC: 7045485. DOI: 10.1186/s12943-020-01168-8. View

11.

Ott P, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N . A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Cell. 2020; 183(2):347-362.e24. DOI: 10.1016/j.cell.2020.08.053. View

12.

Lu J, Xu F, Lu H . LncRNA PVT1 regulates ferroptosis through miR-214-mediated TFR1 and p53. Life Sci. 2020; 260:118305. DOI: 10.1016/j.lfs.2020.118305. View

13.

Zhang K, Ping L, Du T, Liang G, Huang Y, Li Z . A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer. Front Mol Biosci. 2021; 8:678877. PMC: 8215711. DOI: 10.3389/fmolb.2021.678877. View

14.

Yoshida G, Saya H . Molecular pathology underlying the robustness of cancer stem cells. Regen Ther. 2021; 17:38-50. PMC: 8024885. DOI: 10.1016/j.reth.2021.02.002. View

15.

Xu C, Chen Y, Du X, Liu J, Huang C, Chen L . Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ. 2018; 363:k4226. PMC: 6222274. DOI: 10.1136/bmj.k4226. View

16.

Duhen R, Ballesteros-Merino C, Frye A, Tran E, Rajamanickam V, Chang S . Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nat Commun. 2021; 12(1):1047. PMC: 7886909. DOI: 10.1038/s41467-021-21383-1. View

17.

Woo Y, Lee H, Jung Y, Jung Y . Regulated Necrotic Cell Death in Alternative Tumor Therapeutic Strategies. Cells. 2020; 9(12). PMC: 7767016. DOI: 10.3390/cells9122709. View

18.

Andre T, Shiu K, Kim T, Jensen B, Jensen L, Punt C . Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020; 383(23):2207-2218. DOI: 10.1056/NEJMoa2017699. View

19.

Liu H, Hu H, Li G, Zhang Y, Wu F, Liu X . Ferroptosis-Related Gene Signature Predicts Glioma Cell Death and Glioma Patient Progression. Front Cell Dev Biol. 2020; 8:538. PMC: 7363771. DOI: 10.3389/fcell.2020.00538. View

20.

Saga I, Shibao S, Okubo J, Osuka S, Kobayashi Y, Yamada S . Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model. Neuro Oncol. 2014; 16(8):1048-56. PMC: 4096179. DOI: 10.1093/neuonc/nou096. View