A five-gene prognostic signature associated with stromal and immune microenvironment features in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous malignancy characterized by a lack of effective targeted therapies. Precise prognostic stratification and a deep understanding of the tumor microenvironment are critical to optimizing individualized clinical management and prognostic evaluation. Transcriptomic profiles and clinical data of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression and functional enrichment analyses were performed between TNBC tumor tissues and histologically normal adjacent breast tissues. A prognostic model was developed using univariable Cox screening and LASSO Cox regression and was externally assessed in GSE58812. Immune and stromal features were evaluated using xCell2, CIBERSORT, ESTIMATE, GSVA, and pathway-level analyses. A five-gene signature comprising SPRR4, P2RX6, ARHGAP6, IVL, and HES2 was associated with overall survival and showed favorable discrimination in TCGA, with lower 36- and 60-month discrimination in GSE58812. Higher risk scores were associated with stromal enrichment and altered immune-cell composition. The five-gene signature was associated with distinct stromal and immune features and may provide complementary prognostic information in TNBC. Further validation in larger, clinically annotated cohorts is required.