Comprehensive analysis of expression profile and prognostic significance of interferon regulatory factors in pancreatic cancer

Abstract

Background Pancreatic cancer (PC) is a highly lethal disease and an increasing cause of cancer-associated mortality worldwide. Interferon regulatory factors (IRFs) play vital roles in immune response and tumor cellular biological processes. However, the specific functions of IRFs in PC and tumor immune response are far from systematically clarified. This study aimed to explorer the expression profile, prognostic significance, and biological function of IRFs in PC. Results We observed that the levels of IRF2, 6, 7, 8, and 9 were elevated in tumor compared to normal tissues in PC. IRF7 expression was significantly associated with patients’ pathology stage in PC. PC patients with high IRF2, low IRF3, and high IRF6 levels had significantly poorer overall survival. High mRNA expression, amplification and, deep deletion were the three most common types of genetic alterations of IRFs in PC. Low expression of IRF2, 4, 5, and 8 was resistant to most of the drugs or small molecules from Genomics of Drug Sensitivity in Cancer. Moreover, IRFs were positively correlated with the abundance of tumor infiltrating immune cells in PC, including B cells, CD8+ T cells, CD4+ T cells, macrophages, Neutrophil, and Dendritic cells. Functional analysis indicated that IRFs were involved in T cell receptor signaling pathway, immune response, and Toll-like receptor signaling pathway. Conclusions Our results indicated that certain IRFs could serve as potential therapeutic targets and prognostic biomarkers for PC patients. Further basic and clinical studies are needed to validate our findings and generalize the clinical application of IRFs in PC.

Proteogenomic insights into the biology and treatment of pancreatic ductal adenocarcinoma

“…IRF6 is a transcription factor that has been reported to participate in various cellular process through transcription regulation [ 28 ]. Ke Zhang et al have reported that IRF6 might be a prognostic marker in pancreatic cancer [ 29 ]. To gain great insight into the mechanism of how IRF6 led to poor prognosis, we applied correlation analysis on the target genes (TGs) of IRF6.…”