线粒体钙单质蛋白(MCU)是一种跨膜蛋白,可促进钙离子从细胞溶胶进入线粒体。维持钙平衡对于增强细胞能量供应和调节细胞死亡至关重要。通过MCU和钠钙交换剂的钙平衡的相互作用是已知的,但其在乳腺癌肿瘤微环境中的调控仍难以捉摸。需要进一步的研究来探索MCU在BRCA临床病理学中的潜力,肿瘤免疫微环境,和精准肿瘤学。我们的研究,采用多组学方法,将MCU确定为乳腺癌(BRCA)的独立诊断生物标志物,与晚期临床状态和低总生存率相关。利用GEO和TCGA的公共数据集,我们辨别BRCA中差异表达的基因,并检查它们与免疫基因表达的关联,总生存率,肿瘤分期,基因突变状态,和浸润免疫细胞。空间转录组学用于研究BRCA各个区域的MCU基因表达,空间转录组学和单细胞RNA测序方法探讨了MCU与免疫细胞之间的相关性。我们的发现通过对59例BRCA患者样本的分析得到了验证,利用免疫组织化学和生物信息学检查MCU表达之间的关系,临床病理特征,和预后。该研究揭示了BRCA中与遗传变异相关的关键基因调节因子的表达,删除,和肿瘤微环境。这些调节因子的突变与六个免疫数据集中的不同免疫细胞呈正相关,在BRCA的免疫细胞浸润中起关键作用。值得注意的是,高MCU性能与BRCA中CD8+T细胞浸润有关。此外,BRCA细胞系的药物基因组学分析表明,MCU失活与对特定小分子药物的敏感性增加有关.我们的研究结果表明,MCU改变可能与BRCA进展有关,在BRCA中揭示了MCU的新诊断和预后意义。该研究强调了MCU在肿瘤免疫微环境和细胞周期进程中的作用,将其定位为BRCA精准医学和药物筛选的潜在工具。
The mitochondrial calcium uniporter (
MCU) is a transmembrane protein facilitating the entry of calcium ions into mitochondria from the cell cytosol. Maintaining calcium balance is crucial for enhancing cellular energy supply and regulating cell death. The interplay of calcium balance through
MCU and the sodium-calcium exchanger is known, but its regulation in the breast cancer tumor microenvironment remains elusive. Further investigations are warranted to explore MCU\'s potential in BRCA clinical pathology, tumor immune microenvironment, and precision oncology. Our study, employing a multi-omics approach, identifies
MCU as an independent diagnostic biomarker for breast cancer (BRCA), correlated with advanced clinical status and poor overall survival. Utilizing public datasets from GEO and TCGA, we discern differentially expressed genes in BRCA and examine their associations with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. Spatial transcriptomics is employed to investigate MCU gene expression in various regions of BRCA, while spatial transcriptomics and single-cell RNA-sequencing methods explore the correlation between MCUs and immune cells. Our findings are validated through the analysis of 59 BRCA patient samples, utilizing immunohistochemistry and bioinformatics to examine the relationship between MCU expression, clinicopathological features, and prognosis. The study uncovers the expression of key gene regulators in BRCA associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators positively correlate with different immune cells in six immune datasets, playing a pivotal role in immune cell infiltration in BRCA. Notably, high
MCU performance is linked to CD8 + T cells infiltration in BRCA. Furthermore, pharmacogenomic analysis of BRCA cell lines indicates that MCU inactivation is associated with increased sensitivity to specific small molecule drugs. Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for
MCU in BRCA. The study underscores MCU\'s role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening.