研究动态
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MIF 作为三阴性乳腺癌的潜在诊断和预后生物标志物,与 M2 巨噬细胞的极化相关。

MIF as a potential diagnostic and prognostic biomarker for triple-negative breast cancer that correlates with the polarization of M2 macrophages.

发表日期:2024 May 31
作者: Mengting Chen, Hongsen Liu, Bo Hong, Yufei Xiao, Yun Qian
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

巨噬细胞迁移抑制因子(MIF)是一种促炎细胞因子,在抗肿瘤免疫中发挥着至关重要的作用。然而,MIF在影响肿瘤微环境(TME)和三阴性乳腺癌(TNBC)预后中的作用仍有待阐明。使用 R,我们分析了来自 10 个 TNBC 肿瘤样本的 41~567 个细胞的单细胞 RNA 测序 (scRNA-seq) 数据和两名患者的空间转录组数据。使用癌症基因组图谱 (TCGA) 的样本确定了 MIF 表达与免疫细胞浸润、临床病理分期和生存预后之间的关系,并使用免疫组织化学在临床队列中进行了验证。 scRNA-seq数据分析表明,TNBC患者上皮细胞分泌的MIF可以调节巨噬细胞极化为M2表型,这在调节TME中发挥关键作用。空间转录组数据还显示,上皮细胞(肿瘤细胞)和 MIF 位置接近。 TCGA样本分析证实,MIF高表达患者的肿瘤组织富含M2巨噬细胞,并表现出较高的T分期。 MIF 高表达与患者预后不良显着相关。免疫组织化学染色显示高 MIF 表达与年轻患者和较差的临床病理分期相关。上皮细胞分泌的 MIF 可能是 TNBC 诊断和预后的潜在生物标志物,并可能通过重塑肿瘤免疫微环境促进 TNBC 侵袭。© 2024 作者。 FASEB 期刊由 Wiley periodicals LLC 代表美国实验生物学学会联合会出版。
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a crucial role in antitumor immunity. However, the role of MIF in influencing the tumor microenvironment (TME) and prognosis of triple-negative breast cancer (TNBC) remains to be elucidated. Using R, we analyzed single-cell RNA sequencing (scRNA-seq) data of 41 567 cells from 10 TNBC tumor samples and spatial transcriptomic data from two patients. Relationships between MIF expression and immune cell infiltration, clinicopathological stage, and survival prognosis were determined using samples from The Cancer Genome Atlas (TCGA) and validated in a clinical cohort using immunohistochemistry. Analysis of scRNA-seq data revealed that MIF secreted by epithelial cells in TNBC patients could regulate the polarization of macrophages into the M2 phenotype, which plays a key role in modulating the TME. Spatial transcriptomic data also showed that epithelial cells (tumor cells) and MIF were proximally located. Analysis of TCGA samples confirmed that tumor tissues of patients with high MIF expression were enriched with M2 macrophages and showed a higher T stage. High MIF expression was significantly associated with poor patient prognosis. Immunohistochemical staining showed high MIF expression was associated with younger patients and worse clinicopathological staging. MIF secreted by epithelial cells may represent a potential biomarker for the diagnosis and prognosis of TNBC and may promote TNBC invasion by remodeling the tumor immune microenvironment.© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.