Keywords
Immune
IGF2BP1
c-Myc
Submitted : 2024-12-04
Accepted : 2024-12-19
Published : 2025-01-03
Abstract
Glioblastoma multiforme (GBM) is a highly aggressive and lethal brain tumor, with poor patient prognosis and median overall survival of only 10 months despite the current Stupp protocol treatment, due to its high aggressiveness and recurrence rate. This study investigated the role of the IGF2BP1 gene in mesenchymal glioblastoma multiforme (GBM), revealing that IGF2BP1 is upregulated in tumor tissues compared to adjacent normal tissues and positively correlates with MYC gene expression and poor patient prognosis. Immune infiltration analysis showed that IGF2BP1 is associated with specific immune cell populations, and GSVA analysis confirmed its positive correlation with the immune functions of most B cells and macrophages. The mechanism of IGF2BP1 regulating c-Myc expression in mesenchymal GBM and its subsequent impact on immune-related signalling pathways, thereby affecting the immune microenvironment of tumors and patient prognosis, provides new targets and ideas for future immunotherapy of mesenchymal GBM.
References
Śledzińska P, Bebyn MG, Furtak J, et al., 2021, Prognostic and Predictive Biomarkers in Gliomas. International Journal of Molecular Science, 22(19): 10373.
Tan AC, Ashley DM, Lopez GY, et al., 2020, Management of Glioblastoma: State of the Art and Future Directions. CA: Cancer Journal for Clinicinas, 70(4): 299–312.
Marx S, Godicelj A, Wucherpfennig KW, et al., 2022, A Conceptual Framework for Inducing T Cell-Mediated Immunity Against Glioblastoma. Seminars in Immunopathology, 44(5): 697–707.
Molinaro AM, Hervey-Jumper S, Morshed RA, et al., 2020, Association of Maximal Extent of Resection of Contrast-Enhanced and Non-Contrast-Enhanced Tumor with Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma. JAMA Oncology, 6(4): 495–503.
Weller M, Bent M, Preusser M, et al., 2021, EANO Guidelines on the Diagnosis and Treatment of Diffuse Gliomas of Adulthood. Nature Reviews of Clinical Oncology, 18(3): 170–186.
Stupp R, Mason WP, Bent M, et al., 2005, Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma. The New England Journal of Medicine, 352(10): 987–996.
Franceschi E, Minichillo S, Brandes AA, 2017, Pharmacotherapy of Glioblastoma: Established Treatments and Emerging Concepts. CNS Drugs, 31(8): 675–684.
Rhun EL, Preusser M, Roth P, et al., 2019, Molecular Targeted Therapy of Glioblastoma. Cancer Treatment Review, 80: 101896.
Brown MP, Ebert LM, Gargett T, 2019, Clinical Chimeric Antigen Receptor-T Cell Therapy: A New and Promising Treatment Modality for Glioblastoma. Clinical & Translational Immunology, 8(5): e1050.
Brown CE, Alizadeh D, Starr R, et al., 2016, Regression of Glioblastoma After Chimeric Antigen Receptor T-Cell Therapy. The New England Journal of Medicine, 375(26): 2561–2569.
Yuan B, Wang G, Tang X, et al., 2022, Immunotherapy of Glioblastoma: Recent Advances and Future Prospects. Human Vaccines & Immunotherapeutics, 18(5): 2055417.
Feldman L, Brown C, Badie B, 2021, Chimeric Antigen Receptor T-Cell Therapy: Updates in Glioblastoma Treatment. Neurosurgery, 88(6): 1056–1064.
Catalano M, D’ Alessandro G, Trettel F, et al., 2020, Role of Infiltrating Microglia/Macrophages in Glioma. Advances in Experimental Medicine and Biology, 1202: 281–298.
Gutmann DH, Kettenmann H, 2019, Microglia/Brain Macrophages as Central Drivers of Brain Tumor Pathobiology. Neuron, 104(3): 442–449.
Kim Y, Varn FS, Park SH, et al., 2021, Perspective of Mesenchymal Transformation in Glioblastoma. Acta Neuropathologica Communications, 9(1): 50.
Teng J, Hora CC, Kantar RS, et al., 2017, Dissecting Inherent Intratumor Heterogeneity in Patient-Derived Glioblastoma Culture Models. Neuro-Oncology, 19(6): 820–832.
Kim SH, Ezhilarasan R, Philips E, et al., 2016, Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-Dependent Manner. Cancer Cell, 29(2): 201–213.
Mieczkowski J, Kocyk M, Nauman P, et al., 2015, Down-Regulation of IKKβ Expression in Glioma-Infiltrating Microglia/Macrophages Is Associated With Defective Inflammatory/Immune Gene Responses in Glioblastoma. Oncotarget, 6(32): 33077–33090.
Yu MW, Quail DF, 2021, Immunotherapy for Glioblastoma: Current Progress and Challenges. Frontiers in Immunology, 12: 676301.
Jin X, Yin J, Kim SH, et al., 2011, EGFR-AKT-Smad Signaling Promotes Formation of Glioma Stem-like Cells and Tumor Angiogenesis by ID3-Driven Cytokine Induction. Cancer Research, 71(22):7125–7134.
Ah-Pine F, Malaterre-Septembre A, Bedoui Y, et al., 2023, Complement Activation and Up-Regulated Expression of Anaphylatoxin C3a/C3aR in Glioblastoma: Deciphering the Links with TGF-β and VEGF. Cancers (Basel), 15(9):2647.
Fujiwara Y, Komohara Y, Ikeda T, et al., 2011, Corosolic Acid Inhibits Glioblastoma Cell Proliferation by Suppressing the Activation of Signal Transducer and Activator of Transcription-3 and Nuclear Factor-Kappa B in Tumor Cells and Tumor-Associated Macrophages. Cancer Science, 102(1):206–211.
Orozco-Morales M, Sanchez-Garcia FJ, Golan-Cancela I, et al., 2015, RB Mutation and RAS Overexpression Induce Resistance to NK Cell-Mediated Cytotoxicity in Glioma Cells. Cancer Cell International, 15:57.
Lee-Chang C, Rashidi A, Miska J, et al., 2019, Myeloid-Derived Suppressive Cells Promote B Cell-Mediated Immunosuppression via Transfer of PD-L1 in Glioblastoma. Cancer Immunology Research, 7(12):1928–1943.
Weller M, Fontana A, 1995, The Failure of Current Immunotherapy for Malignant Glioma. Tumor-Derived TGF-Beta, T-Cell Apoptosis, and the Immune Privilege of the Brain. Brain Research Reviews, 21(2):128–151.
Kwok D, Okada H, 2020, T-Cell Based Therapies for Overcoming Neuroanatomical and Immunosuppressive Challenges Within the Glioma Microenvironment. Journal of Neurooncology, 147(2):281–295.
Xu S, Tang L, Li X, et al., 2020, Immunotherapy for Glioma: Current Management and Future Application. Cancer Letters, 476:1–12.
Dai XJ, Jiang WJ, Wang WM, et al., 2010, Drug or Vaccine?: Selecting the Appropriate Treatment for Malignant Glioma Patients. Drugs, 70(12):1477–1486.
Miyauchi JT, Tsirka SE, 2018, Advances in Immunotherapeutic Research for Glioma Therapy. Journal of Neurology, 265(4):741–756.
Wang Q, Hu B, Hu X, et al., 2017, Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell, 32(1):42–56.
Neftel C, Laffy J, Filbin MG, et al., 2019, An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. Cell, 178(4):835–849.e21.
Chanoch-Myers R, Wider A, Suva ML, et al., 2022, Elucidating the Diversity of Malignant Mesenchymal States in Glioblastoma by Integrative Analysis. Genome Medicine, 14(1):106.
Doucette T, Rao G, Rao A, et al., 2013, Immune Heterogeneity of Glioblastoma Subtypes: Extrapolation From the Cancer Genome Atlas. Cancer Immunology Research, 1(2):112–122.
Martinez-Lage M, Lynch TM, Bi Y, et al., 2019, Immune Landscapes Associated With Different Glioblastoma Molecular Subtypes. Acta Neuropathologica Communications, 7(1):203.
Du J, Ji H, Ma S, et al., 2021, m6A Regulator-Mediated Methylation Modification Patterns and Characteristics of Immunity and Stemness in Low-Grade Glioma. Briefings in Bioinformatics, 22(5): bbab013.
Jiang X, Liu B, Nie Z, et al., 2021, The Role of m6A Modification in the Biological Functions and Diseases. Signal Transduction and Targeted Theraphy, 6(1):74.
Liu J, Yue Y, Han D, et al., 2014, A METTL3-METTL14 Complex Mediates Mammalian Nuclear RNA N6-Adenosine Methylation. Nature Chemical Biology, 10(2):93–95.
Zhu S, Wang JZ, Chen D, et al., 2020, An Oncopeptide Regulates m6A Recognition by the m6A Reader IGF2BP1 and Tumorigenesis. Nature Communications, 11(1):1685.
Liu P, Zhap P, Li B, et al., 2020, LncRNA PCAT6 Regulated by YY1 Accelerates the Progression of Glioblastoma via miR-513/IGF2BP1. Neurochemical Research, 45(12): 2894–2902.
Liu Y, Guo Q, Yang H, et al., 2022, Allosteric Regulation of IGF2BP1 as a Novel Strategy for the Activation of Tumor Immune Microenvironment. ACS Central Science, 8(8): 1102–1115.
Zhu P, He F, Hou Y, et al., 2021, A Novel Hypoxic Long Noncoding RNA KB-1980E6.3 Maintains Breast Cancer Stem Cell Stemness via Interacting with IGF2BP1 to Facilitate c-Myc mRNA Stability. Oncogene, 40(9): 1609–1627.
Casey SC, Tong L, Li Y, et al., 2016, MYC Regulates the Antitumor Immune Response through CD47 and PD-L1. Science, 352(6282): 227–231.
Li H, Zheng N, Guo A, et al., 2024, FSTL3 Promotes Tumor Immune Evasion and Attenuates Response to Anti-PD1 Therapy by Stabilizing c-Myc in Colorectal Cancer. Cell Death & Disease, 15(2): 107.
Pello OM, Pizzol M, Mirolo M, et al., 2012, Role of c-MYC in Alternative Activation of Human Macrophages and Tumor-Associated Macrophage Biology. Blood, 119(2): 411–421.
Sun X, Zhang T, Li M, et al., 2022, Immunosuppressive B Cells Expressing PD-1/PD-L1 in Solid Tumors: A Mini Review. QJM: Monthly Journal of the Association of Physicians, 115(8): 507–512.
Zaytseva O, Kim N, Quinn LM, et al., 2020, MYC in Brain Development and Cancer. International Journal of Molecular Science, 21(20): 7742.
Gao FY, Li XT, Xu F, et al., 2023, c-MYC Mediates the Crosstalk Between Breast Cancer Cells and Tumor Microenvironment. Cell Communication Signal, 21(1): 28.