4158 - The clinical and transcriptional signatures of human CD204 reveal an applicable marker for tumor associated macrophage in breast cancer

Background

Tumor-associated macrophages (TAMs) constitute over 50% of the number of cells in breast malignancies. In mouse models, most TAMs in the breast cancer microenvironment behave as the M2-like phenotype, with protumor characteristics, but the roles of TAMs in human breast cancer are poorly understand. Specific TAMs related molecular mechanisms among different intrinsic molecular subtypes remain unclear. Here, we focused on studying protumor TAM markers among human breast cancer tissues: CD163, CD204, CD206 which commonly used in mouse models. We identify and explore roles of TAMs novel marker: CD204 in intrinsic molecular subtypes of breast cancer.

Methods

Expression of CD204, CD163, CD206 and clinical outcome of CD204 were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Potential Kyoto Encyclopedia of Genes and Genomes (KEGG) and HALLMARK pathways regulated by CD204 were studied using Gene Set Enrichment Analysis (GSEA). We used CIBERSOT to estimate the immune contextures regulated by CD204 among different subtypes and the correlations of CD204 and immune suppressive molecules were also analyzed.

Results

Compared to CD163, CD206, only CD204 was found upregulated in breast cancer compared to the normal tissue, associated with poor OS, RFS, and DMFS. The expression of CD204 was different between 4 subtypes. CD204 was involved in immune system-related pathways including innate and adaptive immunity among all subtypes. Numerous special pathways were also found influenced by CD204: tumor metabolism-related pathways in luminal A, Hippo and TGF-β signaling pathways in luminal B, cell cycle process in HER-2 amplified, and RIG-I-like receptor signaling pathway in basal-like subtype. Strong correlations between CD204 and immune cells especially for protumor populations were displayed, and most immunosuppressive molecules: HIF1A, FAP, IL10, PDCD1/CD274, CTLA4, HAVCR2, positive correlated with CD204 expression in all subtypes.

Conclusions

CD204 could become an applicable marker of TAMs in human breast cancer. These findings contribute to better understanding and managing of TAMs in different subtypes of breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Jinhai Tang.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.