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

• Published in: Journal of big data Vol. 9; no. 1; p. 88
• Main Authors: Gui, Cheng-Peng, Li, Jia-Ying, Fu, Liang-Min, Luo, Cheng-Gong, Zhang, Chi, Tang, Yi-Ming, Zhang, Li-zhen, Shu, Guan-nan, Wu, Rong-Pei, Luo, Jun-Hang
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 07.07.2022; Springer Nature B.V; SpringerOpen
• Subjects: Antigens; Big Data; Bladder; Bladder cancer; Cancer; Cognition; Communications Engineering; Computational Science and Engineering; Computer Science; Data Mining and Knowledge Discovery; Database Management; Ferroptosis; Gene expression; Immunotherapy; Infiltration; Information Storage and Retrieval; Mathematical Applications in Computer Science; mRNA vaccine; mRNA vaccines; Mutation; Networks; Precise treatment; Prognosis; Tumor immune microenvironment; Tumors; Vaccines; Ferroptosis; Tumor immune microenvironment; Bladder cancer; Immunotherapy; Precise treatment; mRNA vaccine
• DOI: 10.1186/s40537-022-00641-z
• ISSN: 2196-1115

Background The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment. Methods Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients’ ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment. Results Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits. Conclusions TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy.