Research Paper Volume 11, Issue 23 pp 10883—10901

Clinical and transcriptional signatures of human CD204 reveal an applicable marker for the protumor phenotype of tumor-associated macrophages in breast cancer

Yunjie He 1, *, , Siying Zhou 2, *, , Fei Deng 1, *, , Shujie Zhao 3, *, , Wenquan Chen 1, , Dandan Wang 1, , Xiu Chen 1, , Juncheng Hou 1, , Jian Zhang 1, , Wei Zhang 1, , Li Ding 1, , Jinhai Tang 1, , Zuomin Zhou 4, ,

  • 1 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China
  • 2 The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, P.R. China
  • 3 Department of Orthopedic, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210019, P.R. China
  • 4 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, P.R. China
* Equal contribution

received: May 8, 2019 ; accepted: November 17, 2019 ; published: December 4, 2019 ;

https://doi.org/10.18632/aging.102490
How to Cite

Copyright © 2019 He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Tumor-associated macrophages in human breast cancer are poorly understood. Specific tumor-associated macrophage-related molecular mechanisms among different intrinsic molecular subtypes remain unclear. Here, we have identified and explored the roles of the tumor-associated macrophages novel marker: CD204 in different subtypes of breast cancer.

Results: CD204 was upregulated in four subtypes of breast cancer, and this was associated with poor survival outcomes. CD204 could promote tumor cell proliferation, migration, and invasion and was involved in immune system-related pathways among all subtypes. Special pathways in each subtype were also found. High CD204 mRNA expressions were associated with high proportions of protumor immune cell populations, and most immunoinhibitors positive correlated with CD204 expression in all subtypes.

Conclusions: These findings contribute to a better understanding and managing the protumor phenotype of tumor-associated macrophages in different subtypes of breast cancer.

Methods: The expression of CD204 and its clinical outcome were analyzed. The roles of CD204 in the regulation of tumor cell proliferation, migration, and invasion were studied. Potential pathways influenced by CD204 were displayed. Immune cell infiltration in different CD204 mRNA expression status and correlations between CD204 and immunoinhibitors were also analyzed.

Abbreviations

TAMs: tumor associated macrophages; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene Set Enrichment Analysis; TIME: Tumor immune microenvironment; OS: overall survival; RFS: relapse free survival; DMFS: distant metastasis free survival; CAFs: cancer associated fibroblasts; MSR1: macrophage scavenger receptor 1; MDSC: myeloid derived suppressor cells; Iba-1: Ionized calcium-binding adaptor molecule 1.