Abstract
Pancreatic cancer (PC) is a highly fatal and aggressive disease with its incidence and mortality quite discouraging. It is of great significance to construct an effective prognostic signature of PC and find the novel biomarker for the optimization of the clinical decision-making. Due to the crucial role of immunity in tumor development, a prognostic model based on nine immune-related genes was constructed, which was proved to be effective in The Cancer Genome Atlas (TCGA) training set, TCGA testing set, TCGA entire set, GSE78229 set, and GSE62452 set. Furthermore, S100A2 (S100 Calcium Binding Protein A2) was identified as the gene occupying the most paramount position in risk model. Gene set enrichment analysis (GSEA), ESTIMATE and CIBERSORT algorithm revealed that S100A2 was closely associated with the immune status in PC microenvironment, mainly related to lower proportion of CD8+T cells and activated NK cells and higher proportion of M0 macrophages. Meanwhile, patients with high S100A2 expression might get more benefit from immunotherapy according to immunophenoscore algorithm. Afterwards, our independent cohort was also used to demonstrate S100A2 was an unfavorable marker of PC, as well as its remarkably positive correlation with the expression of PD-L1. In conclusion, our results demonstrate S100A2 might be responsible for the preservation of immune-suppressive status in PC microenvironment, which was identified with significant potentiality in predicting prognosis and immunotherapy response in PC patients.