Prognostic Significance of the CXCL11/CXCL9/CD163 Immune Signature in Triple-Negative Breast Cancer: A Bioinformatics and Survival Analysis CXCL11/CXCL9 Prognostic Value

Abstract

Background: Triple-negative breast cancer remains a clinical challenge due to its aggressive nature and poor prognosis. Although it is characterized by a significant immune infiltration, this infiltration often fails to provide protection, requiring precise identification of the genetic hubs driving this failure. This study aimed to identify an immune gene signature associated with favorable prognosis in TNBC using a bioinformatics approach.

Methods: Gene expression data were extracted from the GSE53752 dataset (GEO), GPL13607, includes 51  TNBC tumors and 25 normal tissues, Differential expression analysis was performed. Followed by functional enrichment and protein interaction network (STRING) analysis to identify key immune pathways. Relapse-free survival (RFS) was evaluated for individual genes and for the combined CXCL9/CXCL11/CD163) signature by KM_ Plotter (n = 533) Results: Enrichment analysis demonstrated the dominance of chemokine signaling pathways and the inflammatory response. STRING analysis revealed a robust network centered on chemokines CXCL9, CXCL11, and the macrophage marker CD163. Multivariate Cox regression analysis confirmed that the CXCL9/CXCL11/CD163 signature is an independent predictor significantly associated with a reduced relapse-free survival rate (HR = 0.45; P = 2.3 × 10, indicating a twofold

increase in risk in patients with high signature activation Notably, traditional clinical factors did not reach statistical significance.

Conclusion: In conclusion the CXCL11/CXCL9/CD163 axis represents a strong, independent positive prognostic factor in TNBC. These findings contribute to our understanding of the immune failure mechanisms and confirm that (CXCL11/CXCR3) signal intensity is a key determinant of prognosis, making this axis a promising therapeutic target for modulating the tumor microenvironment.