Identification of mRNA vaccines and conserved ferroptosis related immune landscape for individual precision treatment in bladder cancer

Gui, Chengpeng; Fu, Liangmin; Luo, Chenggong; Zhang, Chi; Tang, Yuanyan; Zhang, Lizhen; Shu, Guannan; Wu, Rongpei; Luo, Junhang

doi:10.1186/s40537-022-00641-z

Cited by 17 publications

(12 citation statements)

References 51 publications

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“…37 Gui recognized six ferroptosis-associated modulators in bladder cancer patients as potential antigens for mRNA vaccine development. 25 Therefore, FRG-based mRNA vaccines are a promising treatment strategy. This appears to be the first investigation identifying FRG-based LGG antigens for developing mRNA vaccines.…”

Section: Discussionmentioning

confidence: 99%

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

Zhao,

Xing,

Guo

et al. 2024

PGPM

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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. Patients and Methods: 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. Results: 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. Conclusion: 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.

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Section: Discussionmentioning

confidence: 99%

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

Zhao,

Xing,

Guo

et al. 2024

PGPM

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“…Gui C et al. established a ferroptosis-induced tumor microenvironment landscape in bladder cancer and identified six genes as potent antigens for developing an anti-BLCA mRNA vaccine ( 52 ). Wang G et al.…”

Section: Discussionmentioning

confidence: 99%

Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer

Zhang

Zhao

et al. 2022

Front. Immunol.

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BackgroundBladder cancer (BLCA) is one of the most prevalent urinary system malignancies, with high mortality and recurrence. The present study aimed to identify potential tumor antigens for mRNA vaccines in BLCA and patient subtypes suitable for different immunotherapy.MethodsGene expression profiles, mutation data, methylation data, and corresponding clinical information were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases. Immunohistochemical staining of microarrays was performed to assess protein expression levels of IGF2BP2 and MMP9. Differential gene analysis, survival analysis, correlation analysis, consensus clustering analysis, and immune cell infiltration analysis were conducted using R software. Finally, the R package “immcluster” was used based on Combat and eXtreme Gradient Boosting algorithms to predict immune clusters of BLCA samples.ResultsTwo mutated, amplified, and over-expressed tumor antigens, IGF2BP2 and MMP9, were found to be associated with clinical outcomes and the abundance of antigen-presenting cells (APCs). Subsequently, three immune subtypes (BIS1, BIS2, and BIS3) were defined in the BLCA cohort. BIS3 subtype exhibited an “active” immune phenotype, while BIS1 and BIS2 subtypes have a “suppressive” immune phenotype. Patients in BIS1 and BIS2 had a poor prognosis compared to BIS3. BIS3 had a higher score in checkpoints or immunomodulators (CP) and immunophenoscore (IPS), while BIS1 and BIS2 scored higher in major histocompatibility complex-related molecules (MHC molecules). Meanwhile, BIS2 and BIS3 had a significantly higher tumor mutational burden (TMB) compared to patients with BIS1. Finally, the “immcluster” package was applied to the dataset, which has been shown to accurately predict the immune subtypes of BLCA samples in many cohorts.ConclusionsIGF2BP2 and MMP9 were potential antigens for developing mRNA vaccines against BLCA. The results in the present study suggested that immunotherapy targeting these two antigens would be suitable for patients falling under the BIS2 subtype. R package “immcluster” could assist in screening suitable BLCA patients for antitumor therapy.

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“…The highrisk BCa group was positively associated with tumor-infiltrating immune cells, including monocytes, fibroblasts, and macrophages, but negatively related to CD4+ T cells and CD8+ T cells [57]. Based on the frlncRNAs related immune landscape, developing anti-BCa mRNA vaccine facilities the individual precision treatment of BCa patients [58].…”

Section: Immune-related Frlncrnas In Urologic Cancermentioning

confidence: 99%

The Roles of Ferroptosis-related Long Non-coding RNAs in Urologic Cancers

Xie

Qin

et al. 2023

ann urol oncol

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Ferroptosis is a type of programmed cell death that has been recent topic of interest in cancer therapy. Growing evidence indicates that long noncoding RNAs (lncRNAs) are involved in ferroptosis and associated with the incidence and progression of cancer. However, the relationship between lncRNA and ferroptosis in urologic cancers has not been fully elucidated. In this review, we summarize ferroptosis-related lncRNAs (frlncRNAs) in urologic cancers. Studies indicate that frlncRNAs are associated with cancer metabolism, tumor microenvironment, and immune cell infiltration. In addition, frlncRNAs could regulate ferroptosis related genes both at the mRNA and protein level. Therefore, a deep understanding of the roles of frlncRNAs in urologic cancers occurrence and progression will provide novel information for the development of anticancer therapies.

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Identification of mRNA vaccines and conserved ferroptosis related immune landscape for individual precision treatment in bladder cancer

Cited by 17 publications

References 51 publications

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer

The Roles of Ferroptosis-related Long Non-coding RNAs in Urologic Cancers

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