Immune-related signature identifies IL1R2 as an immunological and prognostic biomarker in pancreatic cancer.

Objective: Pancreatic cancer is one of the most aggressive malignancies, a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making.

Methods: A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature. Furthermore, the most pivotal gene in the signature was identified. The potential mechanism of the core gene function was revealed through GSEA, CIBERSORT, ESTIMATE, immunophenoscore (IPS) algorithm, single-cell analysis, and functional experiment.

Results: An immune-related prognostic signature and associated nomogram were constructed and validated. Among the genes constituting the signature, interleukin 1 receptor type II (IL1R2) was identified as the gene occupying the most paramount position in the risk signature. Meanwhile, knockdown of IL1R2 significantly inhibited the proliferation, invasion, and migration ability of pancreatic cancer cells. Additionally, high IL1R2 expression was associated with reduced CD8+ T cell infiltration in pancreatic cancer microenvironment, which may be due to high programmed cell death-ligand-1 (PD-L1) expression in cancer cells. Finally, the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy.

Conclusion: In conclusion, our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer, as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.