A novel model combining genes associated with disulfidptosis and glycolysis to predict breast cancer prognosis, molecular subtypes, and treatment response

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-05-15 DOI:10.1002/tox.24329
Mei-Huan Wang, Yue-Hua Gao, Zhen-Dan Zhao, Hua-Wei Zhang
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Abstract

Breast cancer (BC) is a heterogeneous malignancy with a dismal prognosis. Disulfidptosis is a novel type of regulated cell death that happens in the presence of glucose deficiency and is linked to the metabolic process of glycolysis. However, the mechanism of action of disulfidptosis and glycolysis-related genes (DGRG) in BC, as well as their prognostic value in BC patients, remain unknown. After identifying the differentially expressed DGRG in normal and BC tissues, a number of machine learning algorithms were utilized to select essential prognostic genes to develop a model, including SLC7A11, CACNA1H, SDC1, CHST1, and TFF3. The expression characteristics of these genes were then examined using single-cell RNA sequencing, and BC was classified into three clusters using “ConsensusClusterPlus” based on these genes. The DGRG model's median risk score can categorize BC patients into high-risk and low-risk groups. Furthermore, we investigated variations in clinical landscape, immunoinvasion analysis, tumor immune dysfunction and rejection (TIDE), and medication sensitivity in patients in the DGRG model's high- and low-risk groups. Patients in the low-risk group performed better on immunological and chemotherapeutic therapies and had lower TIDE scores. In conclusion, the DGRG model we developed has significant clinical application potential because it can accurately predict the prognosis of BC, TME, and pharmacological treatment responses.

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结合与二硫化钼和糖酵解相关的基因的新型模型,可预测乳腺癌的预后、分子亚型和治疗反应。
乳腺癌(BC)是一种预后不良的异质性恶性肿瘤。二硫化硫是一种新型的调节性细胞死亡,在葡萄糖缺乏时发生,与糖酵解代谢过程有关。然而,二硫化硫和糖酵解相关基因(DGRG)在BC中的作用机制及其在BC患者中的预后价值仍然未知。在确定了正常组织和BC组织中差异表达的DGRG后,研究人员利用多种机器学习算法选择了一些重要的预后基因来建立模型,包括SLC7A11、CACNA1H、SDC1、CHST1和TFF3。然后利用单细胞 RNA 测序检查了这些基因的表达特征,并根据这些基因利用 "ConsensusClusterPlus "将 BC 分成三个群组。DGRG模型的中位风险评分可将BC患者分为高危和低危两组。此外,我们还研究了 DGRG 模型高危组和低危组患者在临床表现、免疫侵袭分析、肿瘤免疫功能障碍和排斥反应(TIDE)以及药物敏感性方面的差异。低风险组患者的免疫和化疗效果更好,TIDE评分更低。总之,我们开发的 DGRG 模型可以准确预测 BC 的预后、TME 和药物治疗反应,因此具有很大的临床应用潜力。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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