Department of Pathology, The First Affiliated Hospital of Henan University of Science and Technology, 471003 Luoyang, Henan, China.
Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, 471003 Luoyang, Henan, China.
Front Biosci (Landmark Ed). 2024 Aug 23;29(8):308. doi: 10.31083/j.fbl2908308.
Aerobic glycolysis and the cell cycle are well-established tumor hallmarks. Understanding their relationship could help to unravel the pathogenic mechanisms of breast cancer (BC) and suggest potential new strategies for treatment.
Glycolysis-related genes (GRGs) were downloaded from the Reactome database and screened using univariate Cox analysis. The consensus clustering method was employed to identify a glycolytic activity signature (GAS) using the Gene Expression Omnibus (GEO) dataset. A nomogram risk prediction model was constructed using coefficients from univariate Cox analysis. Immune cell infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. Gene co-expression modules were created using weighted correlation network analysis (WGCNA) to identify hub genes. Gene expression in three BC cell lines was quantified using Quantitative Reverse Transcriptase Polymera (qRT-PCR). Single-cell RNA sequencing (scRNA-seq) data was used to examine the relationship between GAS and hub genes. The sensitivity of different groups to cell cycle-related clinical drugs was also examined.
BC with high GAS (HGAS) showed high tumor grade and recurrence rate. HGAS was a prognostic indicator of worse overall survival (OS) in BC patients. HGAS BC showed more abundant immune cells and significantly higher expression of immunomodulators compared to BC with low GAS (LGAS). HGAS BC also showed enhanced cell cycle pathway, with high mRNA and protein expression levels of Cyclin B2 (CCNB2), a key component of the cell cycle pathway. Importantly, scRNA-seq analysis revealed that elevated CCNB2 expression was positively correlated with HGAS in triple-negative BC (TNBC). This was validated in clinical samples from TNBC patients. High expression of CCNB2 was found in three BC cell lines, and was also an indicator of poor prognosis. HGAS BC showed high sensitivity to several cell cycle-related clinical drugs, with 9 of these also showing activity in BC with high CCNB2 expression.
HGAS was associated with enhanced cell cycle pathway and immune activity in BC. These results suggest that CCNB2 is a potential key therapeutic target in BC patients.
有氧糖酵解和细胞周期是已确立的肿瘤标志。了解它们之间的关系有助于揭示乳腺癌（BC）的发病机制，并为治疗提供新的潜在策略。
从 Reactome 数据库中下载糖酵解相关基因（GRGs），并使用单变量 Cox 分析进行筛选。使用基因表达综合数据库（GEO）数据集，采用共识聚类方法识别糖酵解活性特征（GAS）。使用单变量 Cox 分析的系数构建列线图风险预测模型。使用单样本基因集富集分析（ssGSEA）和 ESTIMATE 算法评估免疫细胞浸润。使用加权相关网络分析（WGCNA）创建基因共表达模块，以鉴定枢纽基因。使用定量逆转录聚合酶链反应（qRT-PCR）定量三种 BC 细胞系中的基因表达。使用单细胞 RNA 测序（scRNA-seq）数据检查 GAS 与枢纽基因之间的关系。还检查了不同组对细胞周期相关临床药物的敏感性。
GAS 高（HGAS）的 BC 显示出高肿瘤分级和复发率。HGAS 是 BC 患者总生存期（OS）更差的预后指标。与 GAS 低（LGAS）的 BC 相比，HGAS BC 显示出更多的免疫细胞和明显更高的免疫调节剂表达。HGAS BC 还显示出增强的细胞周期途径，细胞周期途径的关键组成部分细胞周期蛋白 B2（CCNB2）的 mRNA 和蛋白表达水平较高。重要的是，scRNA-seq 分析显示，在三阴性乳腺癌（TNBC）中，升高的 CCNB2 表达与 HGAS 呈正相关。这在 TNBC 患者的临床样本中得到了验证。在三种 BC 细胞系中均发现 CCNB2 表达较高，且是预后不良的指标。HGAS BC 对几种细胞周期相关临床药物高度敏感，其中 9 种药物对 CCNB2 表达较高的 BC 也具有活性。
HGAS 与 BC 中增强的细胞周期途径和免疫活性有关。这些结果表明，CCNB2 可能是 BC 患者的潜在关键治疗靶点。
