Department of Breast Surgery, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410006, Hunan, China.
Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210000, China.
Sci Rep. 2024 Oct 24;14(1):25120. doi: 10.1038/s41598-024-76162-x.
Copper-induced cell death is regulated through protein lipoylation, which is critical for gene expression and phenotypic regulation. Neverless, the role of Cuproptosis-related genes in breast cancer (BC) remains unknown. This study aimed to construct a prognostic signature based on the expression of Cuproptosis-related genes in order to guide the diagnosis and treatment for BC. Cuproptosis-related genes prognostic signature has ata of 1250 BC tissues and 583 normal breast tissues were obtained from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and GEO GSE65212. The prognostic signature was established and evaluated with nineteen Cuproptosis-related genes. A series of in silico analyses based on SLC31A1, included expression analysis, independent prognostic analysis, correlation analysis, immune-related analysis and survival analysis. Finally, a series of cell experiments (including quantitative real-time polymerase chain reaction and western blot), and mice experiments were applied to evaluate the impact of SLC31A1 on BC. Cuproptosis-related genes prognostic signature has good predictive promising for survival in BC patients. We discovered that SLC31A1SLC31A1 was overexpressed in BC and was its independent prognostic factor. High expression of the SLC31A1 was correlated with poor prognosis and immune infiltrating of BC. SLC31A1 expression is associated with immune, chemotherapeutic and targeted therapy outcomes in BC. The proliferation, migration, and invasiveness of Her2 + enriched BC cells were decreased by SLC31A1 knockdown, also resulting in a decrease in tumor volume in mouse model. SLC31A1 is a candidate biomarker or therapeutic target in precision oncology, with diagnostic and prognostic significance in BC.
铜诱导的细胞死亡受蛋白脂酰化调控,而蛋白脂酰化对基因表达和表型调节至关重要。然而,铜死亡相关基因在乳腺癌(BC)中的作用尚不清楚。本研究旨在构建基于铜死亡相关基因表达的预后模型,以指导 BC 的诊断和治疗。
从癌症基因组图谱(TCGA)、基因组织表达(GTEx)和 GEO GSE65212 中获得了 1250 份 BC 组织和 583 份正常乳腺组织的数据,用于构建和评估 Cuproptosis 相关基因预后模型。使用 19 个 Cuproptosis 相关基因建立了预后模型,并进行了一系列的计算机分析,包括表达分析、独立预后分析、相关性分析、免疫相关分析和生存分析。最后,进行了一系列的细胞实验(包括实时定量聚合酶链反应和 Western blot)和小鼠实验,以评估 SLC31A1 对 BC 的影响。
Cuproptosis 相关基因预后模型对 BC 患者的生存具有良好的预测潜力。我们发现 SLC31A1 在 BC 中表达上调,是其独立的预后因素。SLC31A1 的高表达与 BC 的不良预后和免疫浸润相关。SLC31A1 的表达与 BC 的免疫、化疗和靶向治疗结果相关。SLC31A1 敲低可降低 Her2 富集型 BC 细胞的增殖、迁移和侵袭能力,同时也可降低小鼠模型中的肿瘤体积。
SLC31A1 是精准肿瘤学中候选的生物标志物或治疗靶点,对 BC 具有诊断和预后意义。