Single-cell sequencing unveils mitophagy-related prognostic model for triple-negative breast cancer.

IF 5.7 2区 医学 Q1 IMMUNOLOGY Frontiers in Immunology Pub Date : 2024-11-04 eCollection Date: 2024-01-01 DOI:10.3389/fimmu.2024.1489444
Peikai Ding, Shengbin Pei, Zheng Qu, Yazhe Yang, Qiang Liu, Xiangyi Kong, Zhongzhao Wang, Jing Wang, Yi Fang
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Abstract

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking hormone receptors and HER2 expression, leading to limited treatment options and poor prognosis. Mitophagy, a selective autophagy process targeting damaged mitochondria, plays a complex role in cancer progression, yet its prognostic significance in TNBC is not well understood.

Methods: This study utilized single-cell RNA sequencing data from the TCGA and GEO databases to identify mitophagy-related genes (MRGs) associated with TNBC. A prognostic model was developed using univariate Cox analysis and LASSO regression. The model was validated across multiple independent cohorts, and correlations between MRG expression, immune infiltration, and drug sensitivity were explored.

Results: Nine key MRGs were identified and used to stratify TNBC patients into high-risk and low-risk groups, with the high-risk group showing significantly worse survival outcomes. The model demonstrated strong predictive accuracy across various datasets. Additionally, the study revealed a correlation between higher MRG expression levels and increased immune cell infiltration, as well as potential responsiveness to specific chemotherapeutic agents.

Conclusion: The mitophagy-related prognostic model offers a novel method for predicting outcomes in TNBC patients and highlights the role of mitophagy in influencing the tumor microenvironment, with potential applications in personalized treatment strategies.

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单细胞测序揭示了与有丝分裂相关的三阴性乳腺癌预后模型。
背景:三阴性乳腺癌(TNBC)是一种缺乏激素受体和HER2表达的侵袭性乳腺癌亚型,其治疗方案有限且预后较差。丝裂吞噬是一种针对受损线粒体的选择性自噬过程,在癌症进展中扮演着复杂的角色,但其在 TNBC 中的预后意义还不甚明了:本研究利用TCGA和GEO数据库中的单细胞RNA测序数据,鉴定与TNBC相关的丝裂吞噬相关基因(MRGs)。利用单变量Cox分析和LASSO回归建立了一个预后模型。该模型在多个独立队列中进行了验证,并探讨了MRG表达、免疫浸润和药物敏感性之间的相关性:结果:确定了九种关键的MRGs,并利用它们将TNBC患者分为高危和低危组,其中高危组的生存结果明显更差。该模型在各种数据集上都表现出很高的预测准确性。此外,研究还揭示了较高的MRG表达水平与免疫细胞浸润增加以及对特定化疗药物的潜在反应性之间的相关性:有丝分裂相关预后模型为预测 TNBC 患者的预后提供了一种新方法,并强调了有丝分裂在影响肿瘤微环境中的作用,有望应用于个性化治疗策略。
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来源期刊
CiteScore
9.80
自引率
11.00%
发文量
7153
审稿时长
14 weeks
期刊介绍: Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.
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