Multi-omics analysis reveals the unique landscape of DLD in the breast cancer tumor microenvironment and its implications for immune-related prognosis

作者：Lijun Xu, Lei Yang, Dan Zhang, Yunxi Wu, Jiali Shan, Huixia Zhu, Zhengyi Lian, Guying He, Chongyu Wang, Qingqing Wang · 发表于：Computational and Structural Biotechnology Journal · 年份：2024 · DOI：10.1016/j.csbj.2024.02.016 · 被引用次数：8 · 研究领域：Ferroptosis and cancer prognosis、Inflammasome and immune disorders、Lipid metabolism and disorders

Abstract Background Cuproptosis, i.e., copper-induced programmed cell death, has potential implications in cancer therapy. However, the impact of the cuproptosis-related gene (CRG) dihydrolipoyl dehydrogenase (DLD) on breast cancer (BC) prognosis remains underexplored. Methods We employed real-time quantitative PCR and multiplexed immunostaining techniques to quantify DLD expression in both BC and the adjacent non-cancerous tissues. Immunofluorescence analysis was employed to assess the influence of DLD on immune cells and immunological checkpoints in the BC microenvironment. DLD knockdown experiments were conducted in BC cell lines MDA-MB-468 and SK-BR-3, with knockdown efficiency validated via western blot. Subsequently, we performed the cell counting kit-8 (CCK-8) assay, clone formation assay, Transwell migration assay, and invasion assay. To construct a prognostic model, we employed a Lasso-Cox regression analysis of immune-related genes associated with DLD. Additionally, we established a competing endogenous RNA network based on CRGs to evaluate potential regulatory pathways. Results Compared to the adjacent tissues, BC tissues exhibited markedly elevated DLD expression levels. In vitro experiments demonstrated that DLD knockdown effectively inhibited BC cell migration, invasion, and proliferation. DLD exhibited positive correlations with CD68 + macrophages and PD-L1 in the tumor, as well as with macrophages and CD4 + T cells in the stroma. Tumor regions with high DLD ex...