Exploring the significance of novel immune-related gene signatures in the prognosis and immune features of pancreatic adenocarcinoma

Abstract Background Immune-related genes (IRGs) are associated with the prognosis of different cancers and are helpful for the diagnosis and management of systematic treatment for cancer patients. However, there have been a few corresponding studies in pancreatic adenocarcinoma (PAAD). Methods The data of PAAD patients were obtained from the TCGA, GEO, and ICGC databases. Additionally, the expression profiles of the normal pancreas from the GTEx database were used to screen differentially expressed immune-related genes (DEIRGs). Cox regression analyses were used to explore overall survival (OS)- and progression-free survival (PFS)-related DEIRGs and to establish two nomograms for PAAD prognosis. Finally, transcription factor (TF), immune infiltration, and unsupervised consensus analyses were performed to understand the potential mechanisms. Results An OS-prognostic signature based on seven DEIRGs and a PFS-prognostic signature based on seven DEIRGs were generated, and their robust prognostic ability was confirmed by ROC curves (OS: 0.736 ~ 0.774, PFS: 0.732 ~ 0.840). According to the risk score, the OS and PFS of the high-risk group were poorer than those of the low-risk group in the training set and four external validation sets. In addition, two nomograms based on the signatures and clinical variables also showed excellent discrimination. And two hub regulatory pathways were successfully validated in several independent datasets. Discernable patterns of DEIRGs in unsupervised consensus analysis showed that patients with low expression of immune checkpoints had a favorable prognosis. Conclusion Two DEIRG-based signatures can be used as independent tools for the prognostic prediction of PAAD and to provide potential novel immunotherapy targets.