Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Int J Mol Sci. 2024 Oct 16;25(20):11114. doi: 10.3390/ijms252011114.
Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and 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 coefficient. Kaplan-Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype ( = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290-0.741; = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS ( = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; < 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; < 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune-inflammatory axis.
白细胞介素在乳腺癌中发挥双重作用，在肿瘤微环境中充当肿瘤发生的促进剂和抑制剂，其炎症功能决定其作用。本研究使用基于微阵列的基因表达分析，分析了急性炎症与慢性炎症白细胞介素特征在乳腺癌亚型中的预后意义。还评估了这些白细胞介素特征与免疫细胞标志物（CD8、IgKC 和 CD20）和免疫检查点（PD-1）之间的相关性。本研究使用 Kaplan-Meier 曲线和 Cox 回归分析，在 461 例早期乳腺癌患者队列中，研究了急性炎症白细胞介素特征（IL-12、IL-21 和 IFN-γ）和慢性炎症白细胞介素特征（IL-4、IL-5、IL-10、IL-13、IL-17 和 CXCL1）对无转移生存（MFS）的预后意义。使用 Spearman-Rho 相关系数分析相关性。Kaplan-Meier 曲线显示，急性炎症白细胞介素特征的预后意义在基底样亚型中尤为明显（ = 0.004，Log Rank）。在多变量 Cox 回归分析中，该特征保留了独立的预后意义（HR 0.463，95%CI 0.290-0.741； = 0.001）。急性炎症白细胞介素特征的高表达与较长的 MFS 相关。慢性炎症白细胞介素特征在整个队列中显示出显著的预后影响，较高的表达与较短的 MFS 相关（ = 0.034）。急性炎症白细胞介素特征与 CD8 表达之间存在显著相关性（ρ=0.391； < 0.001），慢性炎症白细胞介素特征与 PD-1 表达之间存在显著相关性（ρ=0.627； < 0.001）。本研究强调了急性和慢性炎症白细胞介素在乳腺癌进展和预后中的复杂相互作用。这些发现为白细胞介素表达模式在乳腺癌中的预后相关性提供了新的见解，并可能为靶向免疫炎症轴的未来治疗策略提供信息。
