Discovering ferroptosis-associated tumor antigens and ferroptosis subtypes in pancreatic adenocarcinoma to facilitate mRNA vaccine development.

Pancreatic adenocarcinoma (PAAD) is an aggressive, heterogeneous malignancy. We studied the potential of ferroptosis-related tumor vaccines for PAAD treatment. Ferroptosis-related genes, gene expression profiles, and clinical information were extracted from the FerrDB, UCSC Xena, and International Cancer Genome Consortium databases. Differential expression levels and prognostic indices were calculated, genetic alterations and correlations with immune-infiltrating cells were explored, and consensus clustering analysis was performed to identify ferroptosis subtypes and gene modules. Immune enrichment scores were calculated using gene set enrichment analysis, and gene modules were screened using weighted gene co-expression network analysis. The ferroptosis subtype distribution was visualized using graph learning-based dimensionality reduction analysis of the Monocle package with a Gaussian distribution. We identified four ferroptosis-related tumor antigens, AGPS, KDM5A, NRAS, and OSBPL9, which were associated with pancreatic cancer prognosis and antigen-presenting cell infiltration. We determined three minor ferroptosis subtypes, with different clinical prognosis and tumor immune status. Of the subtypes, FS3 may be more suitable for mRNA therapy. We constructed a PAAD ferroptosis landscape to identify the ferroptosis status of patients and predict their prognosis. Finally, we found that the eigengene of the green module was an independent prognostic factor, with a significantly better prognosis in the high-score group than in the low-score group. In conclusion, we identified four ferroptosis-related genes as targets for mRNA vaccines and three ferroptosis subtypes, providing a theoretical basis for the anti-PAAD mRNA vaccine and defining suitable patients for vaccination.