國家衛生研究院 NHRI:Item 3990099045/15781
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    题名: Spatial and single-cell explorations uncover prognostic significance and immunological functions of mitochondrial calcium uniporter in breast cancer
    作者: Li, CJ;Tzeng, YDT;Hsiao, JH;Tseng, LM;Hsu, TS;Chu, PY
    贡献者: National Institute of Cancer Research
    摘要: 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.
    日期: 2024-04-17
    關聯: Cancer Cell International. 2024 Apr 17;24:Article number 140.
    Link to: http://dx.doi.org/10.1186/s12935-024-03327-z
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1475-2867&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001204811200001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85190677123
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