Background/Objectives: Inflammatory breast carcinoma (IBC) is an aggressive and rare neoplasm, accounting for 1–5% of all breast cancers. Toll-like receptor type 4 (TLR4) and Advanced Glycation End Products Receptor (AGER/RAGE) have been implicated in breast cancer, and have been shown to promote tumor growth, metastasis, and resistance to therapy by modulating the tumor microenvironment and inflammatory pathways. However, the role of TLR4 and AGER in IBC has not been elucidated.Methods: TLR4 and AGER immunofluorescence expression were evaluated in 27 IBC and 24 non-IBC samples. The expression data and clinicopathological parameters, including the prognostic values of these biomarkers, were compared.TLR4andAGERgene expression were investigated using the microarray transcriptomic dataset of IBC and non-IBC samples (Gene Expression Omnibus repository—GEO).Results: IBC samples showed higher TLR4 and AGER immunoexpression than the non-IBC group and were associated with obesity and Ki-67 expression (p< 0.05). AGER expression in IBC versus non-IBC was also statistically associated with triple-negative molecular subtypes. Non-IBC subjects with AGER immunoexpression above the cutoff (106.1%, sensitivity of 92.3%, and specificity of 56.2%) showed reduced metastasis-free survival (p= 0.032). In the multivariate analysis, high TLR4 immunostaining increased the risk of metastasis-free survival by 1.029-fold. Analyzing three external GEO datasets confirmed thatTLR4andAGERexpression increased in IBC compared to non-IBC samples.Conclusions: Overall, IBC samples showed higher TLR4 and AGER expressions than other breast cancer types, shedding light on the significance of these markers on IBC biology.
背景/目的：炎性乳腺癌（IBC）是一种侵袭性强且罕见的恶性肿瘤，占所有乳腺癌的1-5%。Toll样受体4（TLR4）和晚期糖基化终末产物受体（AGER/RAGE）已被证实与乳腺癌相关，并通过调节肿瘤微环境和炎症通路促进肿瘤生长、转移及治疗抵抗。然而，TLR4和AGER在IBC中的作用尚未明确。 方法：本研究评估了27例IBC样本和24例非IBC样本中TLR4和AGER的免疫荧光表达情况。对比了表达数据与临床病理参数，包括这些生物标志物的预后价值。同时利用IBC与非IBC样本的微阵列转录组数据集（基因表达综合数据库—GEO）对TLR4和AGER基因表达进行了分析。 结果：IBC样本的TLR4和AGER免疫表达水平高于非IBC组，且与肥胖及Ki-67表达相关（p<0.05）。IBC与非IBC样本中AGER的表达在三阴性分子亚型中也存在统计学关联。AGER免疫表达高于截断值（106.1%，敏感性92.3%，特异性56.2%）的非IBC患者无转移生存期缩短（p=0.032）。多变量分析显示，高TLR4免疫染色使无转移生存风险增加1.029倍。对三个外部GEO数据集的分析证实，与非IBC样本相比，IBC样本中TLR4和AGER表达升高。 结论：总体而言，IBC样本较其他乳腺癌类型表现出更高的TLR4和AGER表达，这为揭示这些标志物在IBC生物学中的意义提供了新的视角。
Clinical Significance and Prognostic Value of TLR4 and AGER in Inflammatory Breast Cancer
肿瘤(癌症)患者之家