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

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.

Hippocampal Transcriptome Changes After Subarachnoid Hemorrhage in Mice

After subarachnoid hemorrhage (SAH), up to 95% of surviving patients suffer from post-SAH syndrome, which includes cognitive deficits with impaired memory, executive functions, and emotional disturbances. Although these long-term cognitive deficits are thought to result from damage to temporomesial–hippocampal areas, the underlying mechanisms remain unknown. To fill this gap in knowledge, we performed a systematic RNA sequencing screen of the hippocampus in a mouse model of SAH. SAH was induced by perforation of the circle of Willis in mice. Four days later, hippocampal RNA was obtained from SAH and control (sham perforation) mice. Next-generation RNA sequencing was used to determine differentially expressed genes in the whole bilateral hippocampi remote from the SAH bleeding site. Functional analyses and clustering tools were used to define molecular pathways. Differential gene expression analysis detected 642 upregulated and 398 downregulated genes (false discovery rate <0.10) in SAH compared to Control group. Functional analyses using IPA suite, Gene Ontology terms, REACTOME pathways, and MsigDB Hallmark gene set collections revealed suppression of oligodendrocytes/myelin related genes, and overexpression of genes related to complement system along with genes associated with innate and adaptive immunity, and extracellular matrix reorganization. Interferon regulatory factors, TGF-β1, and BMP were identified as major orchestrating elements in the hippocampal tissue response. The MEME-Suite identified binding motifs of Krüppel-like factors, zinc finger transcription factors, and interferon regulatory factors as overrepresented DNA promoter motifs. This study provides the first systematic gene and pathway database of the hippocampal response after SAH. Our findings suggest that damage of the entorhinal cortex by subarachnoid blood may remotely trigger specific hippocampal responses, which include suppression of oligodendrocyte function. Identification of these novel pathways may allow for development of new therapeutic approaches for post-SAH cognitive deficits.

Comprehensive Analysis of Expression Profile and Prognostic Significance of Interferon Regulatory Factors in Pancreatic Cancer

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 process. 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 level of IRF3, 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 level 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 biomarker for PC patients. Further basic and clinical studies are needed to validate our findings and generalize the clinical application of IRFs in PC.

An overview of the human immune system and the role of interferon regulatory factors (IRFs)

The immune system consists of a dynamic network of cells, proteins, tissues, and organs that communicate to provide adequate defense responses against pathogenic agents. The immune system divide into the non-specific (innate) and the specific (adaptive) components, where the interactions between these two arms are intricately regulated. To deploy effective immune responses, immune systems comprise various cells and molecules that communicate with each other via signaling pathways coordinated by gene regulatory networks. The interferon regulatory factors (IRFs) are critical regulators of both the immune system’s development and activation of different cells. To better understand the essential components of the normal immune system, this review essentially aims to cover the current knowledge of individual components of the immune system and the important role of IRFs in regulating the immune system.