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

Abstract

Background

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

Methods

      The gene expression data of TNBC from public databases were analyzed to identify differentially expressed genes. Functional enrichment analysis was used to identify active immune pathways. A protein interaction network (STRING) was then constructed to identify gene hubs. To assess clinical significance, Kaplan-Meier survival analysis, restricted to TNBC patients only, was used to evaluate relapse-free survival (RFS) for individual genes and for the combined gene signature (CXCL9, CXCL11, and CD163).

Results

        Enrichment analysis demonstrated the dominance of chemokine signaling pathways and the inflammatory response. STRING analysis revealed a robust network centered around the chemokines CXCL9, CXCL11, and the macrophage marker CD163. Survival analysis showed that high expression of the CXCL11 gene was associated with significantly poor prognosis (P=0.002). Importantly, the combined gene signature demonstrated superior prognostic power, with high expression being associated with significantly poor survival (P=5.3×10−6) and a twofold hazard ratio (HR=0.42). In contrast, other genes such as CD163 and COL10A1 failed to demonstrate independent prognostic significance.