1. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
2. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
3. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China
4. Institute of Pathology, Fudan University, Shanghai, China
5. Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China
6. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
# Equal contribution
Background: Tumor-associated macrophages (TAMs) are one of the most prominent tumor-infiltrating immune cells in the tumor microenvironment (TME) of CRC and play a vital role in the progression of CRC. BST2 was predicted to be associated with the infiltration of TAMs. However, its potential function by which CRC cells and TAMs interact with each other still needs further investigation.
Methods: The target genes in CRC were selected by bioinformatics screening. The level of bone marrow stromal cell antigen 2 (BST2) in CRC cells and tissues was determined by qRT‒PCR, Western blotting, and immunohistochemistry staining. In vitro and in vivo assays were applied to clarify the function of BST2.
Results: In this study, according to bioinformatics analysis, a nomogram based on the risk score (constructed by BST2 and CAV1 (caveolin-1)) and clinical features was built and displayed satisfactory prognostic value. Upregulated BST2 was significantly related to Braf mutation, dMMR/MSI-H, CMS1 subtype, and immune response and was a potential biomarker for predicting immune checkpoint blockade therapy. Silencing BST2 in CRC obviously restrained CRC progression and M2 TAM polarization. The infiltration of TAMs was positively correlated with the high expression of BST2, and depletion of TAMs alleviated the protumoural effect of BST2 in CRC in vivo. In vitro experiments revealed that a reduction in BST2 in CRC inhibited CRC proliferation and migration and also M2 polarization.
Conclusion: These findings indicated that BST2 played a vital role in CRC progression and might be a predictable marker for immunotherapy.
Keywords: BST2, Colorectal cancer (CRC), M2 macrophages, Biomarker