Since interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC. Transcriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein–protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples. Principal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+ T cell and CD68+ macrophages. On account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.

中文翻译：

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干扰素调节因子家族影响结直肠癌患者的肿瘤免疫及预后

由于干扰素调节因子 (IRF) 家族在对病毒感染的免疫反应中起作用，因此之前尚未检查其在结直肠癌 (CRC) 中的作用。本研究试图使用生物信息学方法研究 IRF 家族成员在 CRC 患者的差异表达、生物学功能、肿瘤免疫浸润和临床预后价值方面。从癌症基因组图谱（TCGA）的 COAD/READ 数据集获得 CRC 的转录组谱数据、体细胞突变和临床信息作为训练集。基因表达数据（GSE17536 和 GSE39582）作为验证集从 Gene Expression Omnibus 下载。随机森林算法用于对每个案例的风险进行评分。分析基因和功能富集，构建蛋白质-蛋白质相互作用和非编码RNA网络，通过一系列在线工具和 R 包进行识别中枢基因、表征肿瘤免疫浸润、评估肿瘤突变负荷 (TMB) 和对化学疗法或免疫疗法的敏感性的差异。在组织样本中进行了免疫组织化学 (IHC) 检查。主成分分析 (PCA) 表明，IRF 家族九个成员的转录表达水平在正常结直肠和 CRC 之间存在差异。IRF家族构建的风险评分不仅作为预测具有不同生物学过程、信号通路和TMB的CRC患者生存的独立因素，而且表明不同免疫和基质细胞浸润的不同免疫治疗反应。IRF3 和 IRF7 在 CRC 中上调，表明 CRC 患者的生存时间较短。IRF 家族的差异表达成员表现出不同程度的免疫细胞浸润。IHC 分析显示 IRF3 和 IRF7 表达与肿瘤浸润免疫细胞（包括 CD4+ T 细胞和 CD68+ 巨噬细胞）呈正相关。由于差异表达，IRF 家族成员可以帮助预测 CRC 患者对免疫治疗的反应和临床预后。我们的生物信息学研究不仅提供了遗传特征和肿瘤微环境的初步图片，而且可能为进一步实验探索和验证 CRC 中的 IRF 家族成员提供线索。IHC 分析显示 IRF3 和 IRF7 表达与肿瘤浸润免疫细胞（包括 CD4+ T 细胞和 CD68+ 巨噬细胞）呈正相关。由于差异表达，IRF 家族成员可以帮助预测 CRC 患者对免疫治疗的反应和临床预后。我们的生物信息学研究不仅提供了遗传特征和肿瘤微环境的初步图片，而且可能为进一步实验探索和验证 CRC 中的 IRF 家族成员提供线索。IHC 分析显示 IRF3 和 IRF7 表达与肿瘤浸润免疫细胞（包括 CD4+ T 细胞和 CD68+ 巨噬细胞）呈正相关。由于差异表达，IRF 家族成员可以帮助预测 CRC 患者对免疫治疗的反应和临床预后。我们的生物信息学研究不仅提供了遗传特征和肿瘤微环境的初步图片，而且可能为进一步实验探索和验证 CRC 中的 IRF 家族成员提供线索。