Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer.

Shaoquan Zheng, Yutian Zou, Yuhui Tang, Anli Yang, Jie-Ying Liang, Linyu Wu, Wenwen Tian, Weikai Xiao, Xinhua Xie, Lu Yang, Jindong Xie, Weidong Wei, Xiaoming Xie

Oncoimmunology 2022

filter terms:

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. © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Citation

Shaoquan Zheng, Yutian Zou, Yuhui Tang, Anli Yang, Jie-Ying Liang, Linyu Wu, Wenwen Tian, Weikai Xiao, Xinhua Xie, Lu Yang, Jindong Xie, Weidong Wei, Xiaoming Xie. Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer. Oncoimmunology. 2022;11(1):2020984