Journal
ONCOIMMUNOLOGY
Volume 11, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2021.2020984
Keywords
Triple-negative breast cancer; cancer-associated fibroblast; biglycan; immune microenvironment; extracellular matrix
Categories
Funding
- National Natural Science Foundation of China [82003066]
- Guangzhou Basic and Applied Basic Research Project [202102020168]
- Guangdong Province Basic and Applied Basic Research Fund Project [2020A1515110034]
- Guangzhou Science and Technology Plan Project [202102020114]
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This study reveals the important role of cancer-associated fibroblasts (CAFs) in TNBC and their correlation with tumor progression and the tumor microenvironment. The researchers also identify biglycan (BGN), a soluble secreted protein, as an upregulated marker in CAFs and suggest its potential as a prognostic marker and therapeutic target in TNBC.
Cancer-associated fibroblasts (CAFs) are essential for tumor microenvironment remodeling and correlate with tumor progression. However, interactions between CAFs and tumor cells and immune cells in triple-negative breast cancer (TNBC) are still poorly explored. Here, we investigate the role of CAFs in TNBC and potential novel mediators of their functions. The clustering of classic markers was applied to estimate the relative abundance of CAFs in TNBC cohorts. Primary fibroblasts were isolated from normal and tumor samples. The RNA and culture medium of fibroblasts were subjected to RNA sequencing and mass spectrometry to explore the upregulated signatures in CAFs. Microdissection and single-cell RNA sequencing datasets were used to examine the expression profiles. CAFs were associated with hallmark signalings and immune components in TNBC. Clustering based on CAF markers in the literature revealed different CAF infiltration groups in TNBC: low, medium and high. Most of the cancer hallmark signaling pathways were enriched in the high CAF infiltration group. Furthermore, RNA sequencing and mass spectrometry identified biglycan (BGN), a soluble secreted protein, as upregulated in CAFs compared to normal cancer-adjacent fibroblasts (NAFs). The expression of biglycan was negatively correlated with CD8 + T cells. Biglycan indicated poor prognostic outcomes and might be correlated with the immunosuppressive tumor microenvironment (TME). In conclusion, CAFs play an essential role in tumor progression and the TME. We identified an extracellular protein, biglycan, as a prognostic marker and potential therapeutic target in TNBC.
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