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Abstract：
UNASSIGNED: mRNA vaccines represent a promising and innovative strategy within the realm of cancer immunotherapy. However, their efficacy in treating lower-grade glioma (LGG) requires evaluation. Ferroptosis exhibits close associations with the initiation, evolution, and suppression of cancer. In this study, we explored the landscape of the ferroptosis-associated tumor microenvironment to facilitate the development of mRNA vaccines for LGG patients.
UNASSIGNED: Genomic and clinical data of the LGG patients was obtained from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Ferroptosis-related tumor antigens were identified based on differential expression, mutation status, correlation with antigen-presenting cells, and prognosis, relevance to immunogenic cell death (ICD). Antigen expression levels in LGG specimens and cell lines were validated using real time-polymerase chain reaction (RT-PCR). Consensus clustering was employed for patient classification. The immune landscapes of ferroptosis subtypes were further characterized, including immune responses, prognostic ability, tumor microenvironment, and tumor-related signatures.
UNASSIGNED: Five tumor antigens, namely, HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified in LGG. RT-PCR demonstrated higher expression of these genes in LGG compared to the control. Twelve gene modules and four ferroptosis subtypes (FS1-FS4) of LGG were defined. FS2 and FS4, characterized as \"cold\" tumors due to their decreased tumor mutation burden (TMB) and immune checkpoint proteins (ICPs), were deemed appropriate candidates for the mRNA vaccine.
UNASSIGNED: HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified as promising candidate antigens for the development of an LGG mRNA vaccine, particularly offering potential benefits to FS2 and FS4 patients.
UNASSIGNED: Genomic and clinical data of the LGG patients was obtained from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Ferroptosis-related tumor antigens were identified based on differential expression, mutation status, correlation with antigen-presenting cells, and prognosis, relevance to immunogenic cell death (ICD). Antigen expression levels in LGG specimens and cell lines were validated using real time-polymerase chain reaction (RT-PCR). Consensus clustering was employed for patient classification. The immune landscapes of ferroptosis subtypes were further characterized, including immune responses, prognostic ability, tumor microenvironment, and tumor-related signatures.
UNASSIGNED: Five tumor antigens, namely, HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified in LGG. RT-PCR demonstrated higher expression of these genes in LGG compared to the control. Twelve gene modules and four ferroptosis subtypes (FS1-FS4) of LGG were defined. FS2 and FS4, characterized as \"cold\" tumors due to their decreased tumor mutation burden (TMB) and immune checkpoint proteins (ICPs), were deemed appropriate candidates for the mRNA vaccine.
UNASSIGNED: HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified as promising candidate antigens for the development of an LGG mRNA vaccine, particularly offering potential benefits to FS2 and FS4 patients.
摘要：
■mRNA疫苗代表了癌症免疫疗法领域内的一种有希望和创新的策略。然而,其治疗低度胶质瘤(LGG)的疗效需要评估.铁凋亡与启动密切相关，进化,和抑制癌症。在这项研究中,我们探索了铁凋亡相关肿瘤微环境的景观,以促进LGG患者mRNA疫苗的开发.
■LGG患者的基因组和临床数据来自癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库。根据差异表达鉴定铁凋亡相关肿瘤抗原，突变状态,与抗原呈递细胞的相关性，和预后，与免疫原性细胞死亡（ICD）的相关性。使用实时聚合酶链反应（RT-PCR）验证LGG样本和细胞系中的抗原表达水平。一致性聚类用于患者分类。进一步表征了铁死亡亚型的免疫景观，包括免疫反应，预后能力，肿瘤微环境,和肿瘤相关的特征。
■五种肿瘤抗原，即,HOTAIR,IDO1,KIF20A,在LGG中鉴定出NR5A2和RRM2。与对照相比,RT-PCR证明这些基因在LGG中的表达更高。定义了LGG的12个基因模块和4个铁凋亡亚型（FS1-FS4）。FS2和FS4，由于其降低的肿瘤突变负荷（TMB）和免疫检查点蛋白（ICPs）而被表征为“冷”肿瘤，被认为是mRNA疫苗的合适候选者。
■HOTAIR,IDO1,KIF20A,NR5A2和RRM2被鉴定为开发LGGmRNA疫苗的有希望的候选抗原。特别是为FS2和FS4患者提供潜在益处。
■LGG患者的基因组和临床数据来自癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库。根据差异表达鉴定铁凋亡相关肿瘤抗原，突变状态,与抗原呈递细胞的相关性，和预后，与免疫原性细胞死亡（ICD）的相关性。使用实时聚合酶链反应（RT-PCR）验证LGG样本和细胞系中的抗原表达水平。一致性聚类用于患者分类。进一步表征了铁死亡亚型的免疫景观，包括免疫反应，预后能力，肿瘤微环境,和肿瘤相关的特征。
■五种肿瘤抗原，即,HOTAIR,IDO1,KIF20A,在LGG中鉴定出NR5A2和RRM2。与对照相比,RT-PCR证明这些基因在LGG中的表达更高。定义了LGG的12个基因模块和4个铁凋亡亚型（FS1-FS4）。FS2和FS4，由于其降低的肿瘤突变负荷（TMB）和免疫检查点蛋白（ICPs）而被表征为“冷”肿瘤，被认为是mRNA疫苗的合适候选者。
■HOTAIR,IDO1,KIF20A,NR5A2和RRM2被鉴定为开发LGGmRNA疫苗的有希望的候选抗原。特别是为FS2和FS4患者提供潜在益处。
