Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme

Abstract Immunogenic cell death (ICD), a unique form of cancer cell death, has therapeutic potential in anti-tumour immunotherapy. The aim of this study is to explore the predictive potential of ICD in the prognosis and immunotherapy outcomes of glioblastoma multiforme (GBM). RNA sequencing data and clinical information were downloaded from three databases. Unsupervised consistency clustering analysis was used to identify ICD-related clusters and gene clusters. Additionally, the ICD scores were determined using principal component analysis and the Boruta algorithm via dimensionality reduction techniques. Subsequently, three ICD-related clusters and three gene clusters with different prognoses were identified, with differences in specific tumour immune infiltration-related lymphocytes in these clusters. Moreover, the ICD score was well differentiated among patients with GBM, and the ICD score was considered an independent prognostic factor for patients with GBM. Furthermore, two datasets were used for the external validation of ICD scores as predictors of prognosis and immunotherapy outcomes. The validation analysis suggested that patients with high ICD scores had a worse prognosis. Additionally, a higher proportion of patients with high ICD scores were non-responsive to immunotherapy. Thus, the ICD score has the potential as a biomarker to predict the prognosis and immunotherapy outcomes of patients with GBM.

[1]  Si-di Xie,et al.  A necroptosis-related lncRNA signature was identified to predict the prognosis and immune microenvironment of IDH-wild-type GBM , 2022, Frontiers in Oncology.

[2]  Chao Cheng,et al.  Expression of hub genes of endothelial cells in glioblastoma-A prognostic model for GBM patients integrating single-cell RNA sequencing and bulk RNA sequencing , 2022, BMC Cancer.

[3]  Yan Ma,et al.  Comparative analysis of the prognosis of external beam radiation therapy (EBRT) and EBRT plus brachytherapy for glioblastoma multiforme: a SEER population-based study , 2022, Radiation Oncology.

[4]  Yuelin Zhang,et al.  The prognostic significance of PD-L1 expression in patients with glioblastoma: A meta-analysis , 2022, Frontiers in Oncology.

[5]  Guangxin Ma,et al.  Significance of immunogenic cell death-related genes in prognosis prediction and immune microenvironment landscape of patients with cutaneous melanoma , 2022, Frontiers in Genetics.

[6]  R. He,et al.  Construction of a 5-methylcytosine-Related Molecular Signature to Inform the Prognosis and Immunotherapy of Lung Squamous Cell Carcinoma , 2022, Expert review of molecular diagnostics.

[7]  I. Alnaami,et al.  Impact of Rural vs. Urban Residence on Survival Rates of Patients with Glioblastoma: A Tertiary Care Center Experience , 2022, Brain sciences.

[8]  K. Cao,et al.  Comprehensive development and validation of gene signature for predicting survival in patients with glioblastoma , 2022, Frontiers in Genetics.

[9]  F. Tian,et al.  A genomic instability-associated prognostic signature for glioblastoma patients. , 2022, World neurosurgery.

[10]  Fuxing Zuo,et al.  Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma , 2022, Frontiers in Genetics.

[11]  Xingyu Xiong,et al.  Genomic Analysis Reveals the Prognostic and Immunotherapeutic Response Characteristics of Ferroptosis in Lung Squamous Cell Carcinoma , 2022, Lung.

[12]  Jian Wang,et al.  Characterization of the Immune Cell Infiltration Landscape and a New Prognostic Score in Glioblastoma , 2022, Journal of healthcare engineering.

[13]  Fuqiang Wen,et al.  Analyzing the characteristics of immune cell infiltration in lung adenocarcinoma via bioinformatics to predict the effect of immunotherapy , 2021, Immunogenetics.

[14]  S. Murray,et al.  Glioblastoma: clinical presentation, diagnosis, and management , 2021, BMJ.

[15]  Guohua Yang,et al.  Dissecting Prognosis Modules and Biomarkers in Glioblastoma Based on Weighted Gene Co-Expression Network Analysis , 2021, Cancer management and research.

[16]  A. Addeo,et al.  TMB or not TMB as a biomarker: That is the question. , 2021, Critical reviews in oncology/hematology.

[17]  Fang Cao,et al.  Immune and Clinical Features of CD96 Expression in Glioma by in silico Analysis , 2020, Frontiers in Bioengineering and Biotechnology.

[18]  Jianxun Ding,et al.  Role of nanoparticle-mediated immunogenic cell death in cancer immunotherapy , 2020, Asian journal of pharmaceutical sciences.

[19]  Z. Wang,et al.  Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data for Chinese Glioma Patients , 2020, bioRxiv.

[20]  G. Kroemer,et al.  FLT3LG - a biomarker reflecting clinical responses to the immunogenic cell death inducer oxaliplatin , 2020, Oncoimmunology.

[21]  S. Gerber,et al.  Assessing the Magnitude of Immunogenic Cell Death Following Chemotherapy and Irradiation Reveals a New Strategy to Treat Pancreatic Cancer , 2019, Cancer Immunology Research.

[22]  J. Varner,et al.  Targeting Tumor-Associated Macrophages in Cancer. , 2019, Trends in immunology.

[23]  C. Brennan,et al.  Tumor mutational load predicts survival after immunotherapy across multiple cancer types , 2019, Nature Genetics.

[24]  Yassen Assenov,et al.  Maftools: efficient and comprehensive analysis of somatic variants in cancer , 2018, Genome research.

[25]  Jill S Barnholtz-Sloan,et al.  CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2011-2015. , 2018, Neuro-oncology.

[26]  L. Galluzzi,et al.  Oncogene-induced senescence and tumour control in complex biological systems , 2018, Cell Death & Differentiation.

[27]  Chunsheng Zhang,et al.  Dinaciclib induces immunogenic cell death and enhances anti-PD1–mediated tumor suppression , 2018, The Journal of clinical investigation.

[28]  S. Lipton,et al.  Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 , 2018, Cell Death & Differentiation.

[29]  E. Jaffee,et al.  Tumor Mutational Burden and Response Rate to PD-1 Inhibition. , 2017, The New England journal of medicine.

[30]  F. Lieberman,et al.  Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial , 2017, JAMA.

[31]  J. Rosenberg,et al.  Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  Kaitai Zhang,et al.  Heterogeneity of tumor-infiltrating lymphocytes ascribed to local immune status rather than neoantigens by multi-omics analysis of glioblastoma multiforme , 2017, Scientific Reports.

[33]  M. Weller,et al.  Long-term control and partial remission after initial pseudoprogression of glioblastoma by anti-PD-1 treatment with nivolumab. , 2016, Neuro-oncology.

[34]  K. Chester,et al.  Ipilimumab and Bevacizumab in Glioblastoma. , 2016, Clinical oncology (Royal College of Radiologists (Great Britain)).

[35]  G. Reifenberger,et al.  The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary , 2016, Acta Neuropathologica.

[36]  Eric S. Lander,et al.  Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma , 2016, Cell reports.

[37]  Walter J. Curran,et al.  Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. , 2016, The New England journal of medicine.

[38]  J. Sosman,et al.  Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma , 2016, Cell.

[39]  Lin Feng,et al.  Quantitative proteomics reveals the novel co-expression signatures in early brain development for prognosis of glioblastoma multiforme , 2016, Oncotarget.

[40]  G. Fuller,et al.  PD-L1 expression and prognostic impact in glioblastoma. , 2016, Neuro-oncology.

[41]  D. de Ruysscher,et al.  Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis , 2016, Oncoimmunology.

[42]  A. Louveau,et al.  Revisiting the Mechanisms of CNS Immune Privilege. , 2015, Trends in immunology.

[43]  Steven J. M. Jones,et al.  Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. , 2015, The New England journal of medicine.

[44]  Timothy J Keyes,et al.  Structural and functional features of central nervous system lymphatics , 2015, Nature.

[45]  Satoru Miyano,et al.  Mutational landscape and clonal architecture in grade II and III gliomas , 2015, Nature Genetics.

[46]  X. Dai,et al.  [Malignant transformation of glioma stromal cells induced by glioma stem cells heterotopically inoculated in host liver]. , 2014, Zhonghua yi xue za zhi.

[47]  Caterina Giannini,et al.  Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  G. Getz,et al.  Inferring tumour purity and stromal and immune cell admixture from expression data , 2013, Nature Communications.

[49]  Christina S. Leslie,et al.  CSF-1R inhibition alters macrophage polarization and blocks glioma progression , 2013, Nature Medicine.

[50]  T. Jiang,et al.  Management and survival rates in patients with glioma in China (2004–2010): a retrospective study from a single-institution , 2013, Journal of Neuro-Oncology.

[51]  Vincent J. Lynch,et al.  Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples , 2012, Theory in Biosciences.

[52]  G. Reifenberger,et al.  Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas , 2010, Acta Neuropathologica.

[53]  R. Guillevin,et al.  IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas , 2010, Neurology.

[54]  Witold R. Rudnicki,et al.  Feature Selection with the Boruta Package , 2010 .

[55]  M. J. van de Vijver,et al.  Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. , 2006, Journal of the National Cancer Institute.

[56]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[57]  W. Roa,et al.  Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation , 2002, Acta Neuropathologica.

[58]  Ash A. Alizadeh,et al.  SUPPLEMENTARY NOTE , 1879, Botanical Gazette.

[59]  Ash A. Alizadeh,et al.  Profiling Tumor Infiltrating Immune Cells with CIBERSORT. , 2018, Methods in molecular biology.

[60]  J. Lunceford,et al.  IFN- γ –related mRNA profile predicts clinical response to PD-1 blockade , 2017 .

[61]  Michael Detmar,et al.  A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules , 2015 .

[62]  Cheng Li,et al.  Adjusting batch effects in microarray expression data using empirical Bayes methods. , 2007, Biostatistics.