The Macrophage migration inhibitory factor is a vital player in Pan-Cancer by functioning as a M0 Macrophage biomarker

Yuting Pu; Guifang Yang; Yang Zhou; Xiaogao Pan; Tuo Guo; Xiangping Chai

doi:10.1016/j.intimp.2024.112198

The Macrophage migration inhibitory factor is a vital player in Pan-Cancer by functioning as a M0 Macrophage biomarker

Int Immunopharmacol. 2024 May 10:134:112198. doi: 10.1016/j.intimp.2024.112198. Online ahead of print.

Authors

Yuting Pu¹, Guifang Yang², Yang Zhou³, Xiaogao Pan¹, Tuo Guo¹, Xiangping Chai⁴

Affiliations

¹ Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Emergency Medicine and Difficult Disease Institute, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Emergency Medicine and Difficult Disease Institute, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: yangguifang@csu.edu.cn.
³ Department of Intensive Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Emergency Medicine and Difficult Disease Institute, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: chaixiangping@csu.edu.cn.

PMID: 38733827
DOI: 10.1016/j.intimp.2024.112198

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.

Conclusion: 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.

Keywords: Cancer; Macrophage biomarkers; Macrophage migration inhibitory factor; Malignant tumors; Pan-cancer detection.