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

作者：Chengpeng Gui, Jiaying Li, Liangmin Fu, Chenggong Luo, Chi Zhang, Yiming Tang, Lizhen Zhang, Guannan Shu, Rongpei Wu, Junhang Luo · 发表于：Journal Of Big Data · 年份：2022 · DOI：10.1186/s40537-022-00641-z · 被引用次数：35 · 研究领域：Ferroptosis and cancer prognosis、Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers

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 contr...