Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
BMC Genom Data. 2022 Jan 10;23(1):5. doi: 10.1186/s12863-021-01019-5.
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.
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.
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.
胰腺癌(PC)是一种高度致命的疾病,也是全球癌症相关死亡率上升的一个原因。干扰素调节因子(IRFs)在免疫反应和肿瘤细胞生物学过程中发挥着重要作用。然而,IRFs 在 PC 和肿瘤免疫反应中的具体功能还远未得到系统阐明。本研究旨在探索 IRFs 在 PC 中的表达谱、预后意义和生物学功能。
我们观察到,与正常组织相比,肿瘤组织中 IRF2、6、7、8 和 9 的水平升高。IRF7 的表达与 PC 患者的病理分期显著相关。IRF2、IRF3 和 IRF6 水平高的 PC 患者总生存期明显较差。IRFs 在 PC 中最常见的三种遗传改变类型是 mRNA 表达升高、扩增和深度缺失。IRF2、4、5 和 8 的低表达对癌症基因组药物敏感性分析中的大多数药物或小分子药物耐药。此外,IRFs 与 PC 中肿瘤浸润免疫细胞的丰度呈正相关,包括 B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞。功能分析表明,IRFs 参与了 T 细胞受体信号通路、免疫反应和 Toll 样受体信号通路。
我们的结果表明,某些 IRFs 可以作为 PC 患者潜在的治疗靶点和预后生物标志物。需要进一步的基础和临床研究来验证我们的发现,并推广 IRFs 在 PC 中的临床应用。