Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Immunol. 2024 Nov 4;15:1489444. doi: 10.3389/fimmu.2024.1489444. eCollection 2024.
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.
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.
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.
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.
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，导致治疗选择有限，预后较差。线粒体自噬是一种靶向受损线粒体的选择性自噬过程，在癌症进展中发挥着复杂的作用，但在 TNBC 中的预后意义尚不清楚。
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 相关的线粒体自噬相关基因（MRGs）。采用单因素 Cox 分析和 LASSO 回归构建预后模型。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。
鉴定出 9 个关键的 MRGs，用于将 TNBC 患者分为高危和低危组，高危组的生存结果明显较差。该模型在各种数据集上均具有较强的预测准确性。此外，研究还揭示了较高的 MRG 表达水平与增加的免疫细胞浸润之间存在相关性，以及对特定化疗药物的潜在反应性。
线粒体自噬相关的预后模型为预测 TNBC 患者的预后提供了一种新方法，并强调了线粒体自噬在影响肿瘤微环境中的作用，具有潜在的个性化治疗策略应用价值。
