关键词: Breast cancer Diagnostic biomarker OPA Spatial transcriptomic immune cell

来  源:   DOI:10.7150/jca.96100   PDF(Pubmed)

Abstract:
Background: As we delve into the intricate world of mitochondrial inner membrane proteins, particularly Optic Atrophy types 1 and 3 (OPA1/3), we uncover their pivotal role in maintaining mitochondrial dynamic equilibrium and fusion, crucial for cellular energy production and synthesis. Despite extensive scrutiny, the significance of OPA1/3 in breast cancer (BRCA) and its interplay with the immune microenvironment remain elusive. Materials and Methods: We meticulously sourced BRCA data from renowned repositories such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA), leveraging cutting-edge techniques including single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and pharmacogenomics. Through multifaceted data analysis, we endeavored to unravel the intricate role and potential value of OPA1/3 in BRCA tumorigenesis and progression. Results: Our investigation reveals a conspicuous upregulation of OPA1/3 expression in BRCA, correlating with dismal prognoses. Kaplan-Meier plot analysis underscores that heightened OPA1/3 levels are associated with poor survival rates. Both clinical specimens and biobank biopsies corroborate the elevated expression of OPA1/3 in breast cancer patients. Moreover, scRNA-seq unveils a strong correlation between OPA1/3 and macrophage infiltration in the BRCA immune milieu, alongside its association with the cellular communication network involving CXCL, TGFb, VEGF, and IL16. Conclusion: In light of these findings, OPA1/3 emerges as a promising contender for therapeutic targeting and as a potential diagnostic, prognostic, and survival biomarker in BRCA. The implications of our study underscore the pressing need to explore these novel biomarkers to enhance patient outcomes.
摘要:
背景:当我们深入研究线粒体内膜蛋白的复杂世界时,特别是1型和3型光学萎缩(OPA1/3),我们发现它们在维持线粒体动态平衡和融合中的关键作用,对于细胞能量生产和合成至关重要。尽管进行了广泛的审查,OPA1/3在乳腺癌(BRCA)中的意义及其与免疫微环境的相互作用仍然难以捉摸。材料和方法:我们从著名的数据库中精心获取BRCA数据,如癌症基因组图谱(TCGA),基因型-组织表达(GTEx),基因表达综合(GEO),和人类蛋白质图谱(HPA),利用尖端技术,包括单细胞RNA测序(scRNA-seq),空间转录组学,和药物基因组学。通过多方面的数据分析,我们致力于揭示OPA1/3在BRCA肿瘤发生和发展中的复杂作用和潜在价值.结果:我们的调查显示,BRCA中OPA1/3的表达明显上调,与悲观的预后有关。Kaplan-Meier图分析强调了升高的OPA1/3水平与低生存率相关。临床标本和生物样本库活检证实了乳腺癌患者中OPA1/3的表达升高。此外,scRNA-seq揭示了BRCA免疫环境中OPA1/3与巨噬细胞浸润之间的强相关性,除了它与涉及CXCL的蜂窝通信网络的关联之外,TGFb,VEGF,IL16结论:根据这些发现,OPA1/3成为治疗靶向和潜在诊断的有希望的竞争者,预后,和BRCA中的生存生物标志物。我们研究的意义强调了探索这些新型生物标志物以提高患者预后的迫切需要。
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