Liu Gang, Yu Guozheng, Yin Dongzhi, Ma Jianying
Department of Thyroid and Breast Surgery, The People's Hospital of Suzhou New District, Suzhou, China.
Department of Breast Surgery, Thyroid Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No.141, Tianjin Road, Huangshi, 435000, Hubei, China.
Sci Rep. 2025 Feb 25;15(1):6794. doi: 10.1038/s41598-025-91613-9.
Mitophagy is an essential cellular process that is conserved and crucial for maintaining cellular balance by selectively eliminating malfunctioning mitochondria. However, there is still limited knowledge regarding the influence of mitophagy-related genes (MRGs) on the prognosis and response to treatment of triple-negative breast cancer (TNBC). In here, the TCGA and GEO databases were used to acquire the transcriptomic and clinical information of patients with TNBC, correspondingly. Using LASSO and multivariable Cox regression analyses, a risk signature related to mitophagy was established based on the prognostic MRGs. The prognostic signature associated with mitophagy consisted of five genes (BSG, JMJD6, DNAJA3, DISC1, and SQSTM1) and independently predicted the prognosis of patients with TNBC, regardless of clinical factors (p < 0.05). Patients classified within the high-risk group demonstrated significantly lower overall survival rates when contrasted with those in the low-risk group. The model exhibited excellent performance in predicting survival and risk stratification, as evidenced by the receiver operating characteristic and C-index. The findings stayed unchanged following external validation. Moreover, we observed a notable variation in the tumor immune microenvironment among the different risk categories. Patients with a low risk of TNBC demonstrated a more favorable response to immunotherapy compared to patients with a high risk. In conclusion, our study uncovered the possible impacts of MRGs on the tumor microenvironment, clinical and pathological characteristics, and outlook of TNBC. The CRG-related signature was strongly linked to the immune response against TNBC and has the potential to serve as a valuable tool in predicting the prognosis and immunotherapy response of patients.
线粒体自噬是一种重要的细胞过程，它通过选择性清除功能异常的线粒体来维持细胞平衡，这一过程在进化上保守且至关重要。然而，关于线粒体自噬相关基因（MRGs）对三阴性乳腺癌（TNBC）预后及治疗反应的影响，目前仍知之甚少。在此，我们利用TCGA和GEO数据库分别获取TNBC患者的转录组信息和临床信息。通过LASSO和多变量Cox回归分析，基于预后MRGs建立了一个与线粒体自噬相关的风险特征。与线粒体自噬相关的预后特征由五个基因（BSG、JMJD6、DNAJA3、DISC1和SQSTM1）组成，并且无论临床因素如何（p < 0.05），都能独立预测TNBC患者的预后。与低风险组患者相比，高风险组患者的总生存率显著更低。该模型在预测生存和风险分层方面表现优异，这在受试者工作特征曲线和C指数中得到了证实。外部验证后，研究结果保持不变。此外，我们观察到不同风险类别之间肿瘤免疫微环境存在显著差异。与高风险TNBC患者相比，低风险患者对免疫治疗的反应更佳。总之，我们的研究揭示了MRGs对TNBC肿瘤微环境、临床病理特征及预后的潜在影响。与CRG相关的特征与针对TNBC的免疫反应密切相关，并且有潜力作为预测患者预后和免疫治疗反应的有价值工具。
