Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients’ survival

• Published in: Therapeutic advances in medical oncology 2022-01, Vol.14, p.17588359221127678-17588359221127678
• Main Authors: Moreno, Daniel Antunes, da Silva, Luciane Sussuchi, Gomes, Isabella, Leal, Letícia Ferro, Berardinelli, Gustavo Noriz, Gonçalves, Gisele Melo, Pereira, Caio Augusto, Santana, Iara Viana Vidigal, Matsushita, Marcus de Medeiros, Bhat, Krishna, Lawler, Sean, Reis, Rui Manuel
• Format: Article
• Language: English
• Subjects: Apoptosis; Astrocytoma; Biomarkers; Brain cancer; Brain tumors; Cancer; Cancer immunotherapy; CD45 antigen; Cytotoxicity; Gene expression; Genomes; Genomic Biomarkers in Cancer Immunotherapy; Glioblastoma; Immunology; Isocitrate dehydrogenase; Macrophages; Medical prognosis; Microenvironments; Oncology; Paraffin; PD-L1 protein; Phenotypes; Tumors
• ISSN: 1758-8359; 1758-8340; 1758-8359
• DOI: 10.1177/17588359221127678

Introduction: Glioblastoma (GBM), isocitrate dehydrogenase (IDH) wild-type (IDHwt), and grade 4 astrocytomas, IDH mutant (IDHmut), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities. Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDHwt GBM and IDHmut tumors and identify prognostic biomarkers and a gene signature associated with patient survival. Methods: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator). Results: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDHwt GBM compared to IDHmut tumors. Regarding IDHwt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1). Conclusion: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDHwt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients’ prognosis.