Abstract：
BACKGROUND: The role of the macrophage migration inhibitory factor (MIF) has recently attracted considerable attention in cancer research; nonetheless, the insights provided by current investigations remain constrained. Our main objective was to investigate its role and the latent mechanisms within the pan-cancer realm.
METHODS: We used comprehensive pan-cancer bulk sequencing data and online network tools to investigate the association between MIF expression and patient prognosis, genomic instability, cancer cell stemness, DNA damage repair, and immune infiltration. Furthermore, we validated the relationship between MIF expression and M0 macrophages using single-cell datasets, the SpatialDB database, and fluorescence staining. Additionally, we assessed the therapeutic response using the ROC plotter tool.
RESULTS: We observed the upregulation of MIF expression across numerous cancer types. Notably, elevated MIF levels were associated with a decline in genomic stability. We found a significant correlation between increased MIF expression and increased expression of mismatch repair genes, stemness features, and homologous recombination genes across diverse malignancies. Subsequently, through an analysis using ESTIMATE and cytokine results, we revealed the involvement of MIF in immune suppression. Then, we validated MIF as a hallmark of the M0 macrophages involved in tumor immunity. Our study suggests an association with other immune-inhibitory cellular populations and restraint of CD8 + T cells. In addition, we conducted a comparative analysis of MIF expression before and after treatment in three distinct sets of therapy responders and non-responders. Intriguingly, we identified notable disparities in MIF expression patterns in bladder urothelial carcinoma and ovarian cancer following particular therapeutic interventions.
CONCLUSIONS: Comprehensive pan-cancer analysis revealed notable enrichment of MIF within M0 macrophages, exerting a profound influence on tumor-associated immunosuppression and the intricate machinery of DNA repair.
METHODS: We used comprehensive pan-cancer bulk sequencing data and online network tools to investigate the association between MIF expression and patient prognosis, genomic instability, cancer cell stemness, DNA damage repair, and immune infiltration. Furthermore, we validated the relationship between MIF expression and M0 macrophages using single-cell datasets, the SpatialDB database, and fluorescence staining. Additionally, we assessed the therapeutic response using the ROC plotter tool.
RESULTS: We observed the upregulation of MIF expression across numerous cancer types. Notably, elevated MIF levels were associated with a decline in genomic stability. We found a significant correlation between increased MIF expression and increased expression of mismatch repair genes, stemness features, and homologous recombination genes across diverse malignancies. Subsequently, through an analysis using ESTIMATE and cytokine results, we revealed the involvement of MIF in immune suppression. Then, we validated MIF as a hallmark of the M0 macrophages involved in tumor immunity. Our study suggests an association with other immune-inhibitory cellular populations and restraint of CD8 + T cells. In addition, we conducted a comparative analysis of MIF expression before and after treatment in three distinct sets of therapy responders and non-responders. Intriguingly, we identified notable disparities in MIF expression patterns in bladder urothelial carcinoma and ovarian cancer following particular therapeutic interventions.
CONCLUSIONS: Comprehensive pan-cancer analysis revealed notable enrichment of MIF within M0 macrophages, exerting a profound influence on tumor-associated immunosuppression and the intricate machinery of DNA repair.
摘要：
背景：巨噬细胞移动抑制因子（MIF）的作用最近在癌症研究中引起了相当大的关注；尽管如此，当前调查提供的见解仍然受到限制。我们的主要目标是研究其在泛癌症领域中的作用和潜在机制。
方法：我们使用全面的泛癌症批量测序数据和在线网络工具来调查MIF表达与患者预后之间的关联。基因组不稳定性，癌细胞的干细胞，DNA损伤修复,和免疫浸润。此外，我们使用单细胞数据集验证了MIF表达与M0巨噬细胞之间的关系，SpatialDB数据库，和荧光染色。此外,我们使用ROC绘图仪评估治疗反应.
结果：我们观察到多种癌症类型中MIF表达的上调。值得注意的是,MIF水平升高与基因组稳定性下降相关.我们发现MIF表达增加和错配修复基因表达增加之间存在显著相关性,干性特征，以及跨越不同恶性肿瘤的同源重组基因。随后，通过使用估计和细胞因子结果的分析，我们揭示了MIF参与免疫抑制。然后，我们验证了MIF是参与肿瘤免疫的M0巨噬细胞的标志.我们的研究表明与其他免疫抑制细胞群和CD8+T细胞的抑制有关。此外,我们对三组不同的治疗应答者和非应答者治疗前后的MIF表达进行了比较分析.有趣的是，我们发现膀胱尿路上皮癌和卵巢癌在特定治疗干预后MIF表达模式存在显著差异.
结论：全面的泛癌症分析显示M0巨噬细胞中MIF的显著富集，对肿瘤相关的免疫抑制和复杂的DNA修复机制产生深远的影响。
方法：我们使用全面的泛癌症批量测序数据和在线网络工具来调查MIF表达与患者预后之间的关联。基因组不稳定性，癌细胞的干细胞，DNA损伤修复,和免疫浸润。此外，我们使用单细胞数据集验证了MIF表达与M0巨噬细胞之间的关系，SpatialDB数据库，和荧光染色。此外,我们使用ROC绘图仪评估治疗反应.
结果：我们观察到多种癌症类型中MIF表达的上调。值得注意的是,MIF水平升高与基因组稳定性下降相关.我们发现MIF表达增加和错配修复基因表达增加之间存在显著相关性,干性特征，以及跨越不同恶性肿瘤的同源重组基因。随后，通过使用估计和细胞因子结果的分析，我们揭示了MIF参与免疫抑制。然后，我们验证了MIF是参与肿瘤免疫的M0巨噬细胞的标志.我们的研究表明与其他免疫抑制细胞群和CD8+T细胞的抑制有关。此外,我们对三组不同的治疗应答者和非应答者治疗前后的MIF表达进行了比较分析.有趣的是，我们发现膀胱尿路上皮癌和卵巢癌在特定治疗干预后MIF表达模式存在显著差异.
结论：全面的泛癌症分析显示M0巨噬细胞中MIF的显著富集，对肿瘤相关的免疫抑制和复杂的DNA修复机制产生深远的影响。
