Prognostic Impact of Pro- and Anti-Inflammatory Interleukin mRNA-Expression Signatures in Early Breast Cancer

Background: Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, which is shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of anti-inflammatory and pro-inflammatory signatures using microarray-based gene ex-pression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, CD20) and immune checkpoints (PD-1) were also evaluated. Materials and Methods: The study investigated the prognostic significance of an an-ti-inflammatory interleukin signature (IL-12, IL-21, IFN-γ) and a pro-inflammatory inter-leukin signature (IL-4, IL-5, IL-10, IL-13, IL-17, CXCL1) for metastasis-free survival (MFS) using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coef-ficient. Results: Kaplan-Meier curves revealed that the prognostic significance of the an-ti-inflammatory signature was specifically pronounced in the basal-like subtype (p=0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290-0.741; p=0.001). Higher expression of the anti-inflammatory interleukin signature was associated with longer MFS. The pro-inflammatory interleukin signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p=0.034). Strong cor-relations were found between the anti-inflammatory signature and CD8 expression (ρ=0.391; p