Background: The tumor microenvironment (TME) in breast cancer plays a vital role in occurrence, development, and therapeutic responses. However, immune and stroma constituents in the TME are major obstacles to understanding and treating breast cancer. We evaluated the significance of TME-related genes in breast cancer.
Methods: Invasive breast cancer (BRCA) samples were retrieved from the TCGA and GEO databases. Stroma and immune scores of samples as well as the proportion of tumor infiltrating immune cells (TICs) were calculated using the ESTIMATE and CIBERSORT algorithms. TME-related differentially expressed genes (DEGs) were analyzed by a protein interaction (PPI) network and univariate Cox regression to determine CD1C as a hub gene. Subsequently, the prognostic value of CD1C, its response to immunotherapy, and its mechanism in the TME were further studied.
Results: In BRCA, DEGs were determined to identify CD1C as a hub gene. The expression level of CD1C in BRCA patients was verified based on the TCGA database, polymerase chain reaction (PCR) results, and western blot analysis. Immunohistochemical staining (IHC) results revealed a correlation between prognosis, clinical features, and CD1C expression in BRCA. Enrichment analysis of GSEA and GSVA showed that CD1C participates in immune-associated signaling pathways. CIBERSORT showed that CD1C levels were associated with tumor immune infiltrating cells (TILs), such as different kinds of T cells. Gene co-expression analysis showed that CD1C and the majority of immune-associated genes were co-expressed in BRCA. In renal cell carcinoma, patients with a high expression of CD1C had a better immunotherapy effect.
Conclusion: CD1C is an important part of the TME and participates in immune activity regulation in breast tumors. CD1C is expected to become a prognostic marker and a new treatment target for breast cancer.
Keywords: Breast cancer; CD1C; CIBERSORT algorithm; ESTIMATE algorithm; Tumor microenvironment.
© 2023. The Author(s).