Yu Bing, Xing Zhimei, Tian Xiaoxuan, Feng Rui
Department of Breast Surgery, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, People's Republic of China.
State Key Laboratory of Component‑Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People's Republic of China.
Breast Cancer (Dove Med Press). 2024 Sep 2;16:529-544. doi: 10.2147/BCTT.S475007. eCollection 2024.
Triple-negative breast cancer (TNBC) is recognized as the most aggressive molecular subtype of breast cancer. Recent studies have highlighted the complex role of autophagy in the pathogenesis of TNBC.
In this study, we evaluated 18,330 genes, including 1111 autophagy-related genes, (ARGs), across 579 TNBC samples from online databases. Differentially expressed ARGs in TNBC were identified using high-throughput RNA-seq data from the Cancer Genome Atlas (TCGA). Prognostic factors were examined through Cox regression and multivariate Cox analyses, with predictive efficacy assessed using receiver operating characteristic (ROC) curves. A nomogram integrating the risk signature with clinicopathological factors, such as TNM stage, was developed. Immunohistochemical analysis of clinical samples was also conducted.
EIF4EBP1 and NPAS3 were significantly correlated with prognostic outcomes in patients with TNBC. Multivariate Cox regression analysis demonstrated that the expression levels of these two genes were accurate predictors of disease progression in TNBC samples from TCGA and the GSE31519 dataset. The efficacy of this predictive model was validated using ROC curve analysis and calibration plots, confirming its ability to accurately estimate the 1-, 2-, and 3-year survival rates for individuals with TNBC. Additionally, EIF4EBP1 and NPAS3 expression influenced drug sensitivity in TNBC cell lines, with notably lower NPAS3 expression in TNBC tissues, particularly in Stage III cases. This study is the first to report NPAS3 expression in patients with TNBC.
The autophagy-related genes EIF4EBP1 and NPAS3 may serve as independent prognostic factors for individuals with TNBC.
三阴性乳腺癌（TNBC）被认为是乳腺癌中最具侵袭性的分子亚型。最近的研究强调了自噬在TNBC发病机制中的复杂作用。
在本研究中，我们从在线数据库评估了579个TNBC样本中的18330个基因，包括1111个自噬相关基因（ARGs）。使用来自癌症基因组图谱（TCGA）的高通量RNA测序数据鉴定TNBC中差异表达的ARGs。通过Cox回归和多变量Cox分析检查预后因素，并使用受试者工作特征（ROC）曲线评估预测效能。开发了一个将风险特征与临床病理因素（如TNM分期）相结合的列线图。还对临床样本进行了免疫组织化学分析。
EIF4EBP1和NPAS3与TNBC患者的预后结果显著相关。多变量Cox回归分析表明，这两个基因的表达水平是TCGA和GSE31519数据集中TNBC样本疾病进展的准确预测指标。使用ROC曲线分析和校准图验证了该预测模型的效能，证实其能够准确估计TNBC个体的1年、2年和3年生存率。此外，EIF4EBP1和NPAS3的表达影响TNBC细胞系中的药物敏感性，TNBC组织中NPAS3的表达明显较低，尤其是在III期病例中。本研究首次报道了TNBC患者中NPAS3的表达。
自噬相关基因EIF4EBP1和NPAS3可能是TNBC个体的独立预后因素。
