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.

机构信息

Department of Clinical Laboratory, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China.

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China.

出版信息

FASEB J. 2024 May 31;38(10):e23696. doi: 10.1096/fj.202400578R.

DOI:10.1096/fj.202400578R

PMID:38787620

Abstract

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.

摘要

巨噬细胞移动抑制因子（MIF）是一种促炎细胞因子，在抗肿瘤免疫中发挥着关键作用。然而，MIF 影响三阴性乳腺癌（TNBC）肿瘤微环境（TME）和预后的作用仍有待阐明。我们使用 R 分析了来自 10 个 TNBC 肿瘤样本的 41567 个细胞的单细胞 RNA 测序（scRNA-seq）数据和来自两名患者的空间转录组数据。使用癌症基因组图谱（TCGA）中的样本确定了 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，并通过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 可以调节巨噬细胞向 M2 表型的极化，这在调节 TME 中起着关键作用。空间转录组数据还显示上皮细胞（肿瘤细胞）和 MIF 位置接近。对 TCGA 样本的分析证实，高 MIF 表达的肿瘤组织富含 M2 巨噬细胞，且 T 分期更高。高 MIF 表达与患者预后不良显著相关。免疫组化染色显示，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 可能代表 TNBC 诊断和预后的潜在生物标志物，并且可能通过重塑肿瘤免疫微环境促进 TNBC 的侵袭。