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基于铜死亡相关模式的预测乳腺癌患者生存、免疫浸润和免疫治疗疗效的预后模型的构建:基于铜死亡的乳腺癌预后模型构建。

Construction of a prognostic model based on cuproptosis-related patterns for predicting survival, immune infiltration, and immunotherapy efficacy in breast cancer: Cuproptosis-based prognostic modeling in breast cancer.

机构信息

Department of Breast Neoplastic Surgery, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

出版信息

Medicine (Baltimore). 2024 Nov 1;103(44):e40136. doi: 10.1097/MD.0000000000040136.

Abstract

Breast cancer is the most common and lethal malignancy among women worldwide. Cuproptosis, a newly identified copper-dependent cell death, is closely associated with cancer development. However, its regulatory mechanisms in breast cancer are not well studied. This study aims to establish a prognostic model for breast cancer to improve risk stratification. The mRNA expression data was downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Consensus clustering identified patterns based on cuproptosis-related genes. Key genes were screened using Weighted Gene Co-Expression Network Analysis and differentially expressed gene analysis. A prognostic model was constructed using Cox regression and evaluated with time-dependent receiver operating characteristic and Kaplan-Meier analyses. Functional pathways, immune cell infiltration, and other tumor characteristics were also analyzed. Two distinct cuproptosis patterns were identified. The top 21 differentially expressed genes, significantly associated with survival, were used to construct the prognostic model. The risk score has a negative correlation with survival. Enrichment analysis showed immune-related pathways enriched in the low-risk group, which also had more immune cell infiltration, higher stromal component, lower tumor purity, and lower tumor heterogeneity. Finally, significant differences of half maximal inhibitory concentration were also observed between patients in high- and low-risk groups who received chemotherapy and targeted therapy drugs. These findings in our study may provide evidence for further research and individualized management of breast cancer.

摘要

乳腺癌是全球女性中最常见和最致命的恶性肿瘤。铜死亡是一种新发现的铜依赖性细胞死亡,与癌症的发生密切相关。然而,其在乳腺癌中的调控机制尚未得到充分研究。本研究旨在建立乳腺癌的预后模型,以改善风险分层。从癌症基因组图谱和基因表达综合数据库中下载了 mRNA 表达数据。共识聚类根据铜死亡相关基因确定了模式。使用加权基因共表达网络分析和差异表达基因分析筛选关键基因。使用 Cox 回归构建预后模型,并通过时间依赖性接收者操作特征和 Kaplan-Meier 分析进行评估。还分析了功能途径、免疫细胞浸润和其他肿瘤特征。确定了两种不同的铜死亡模式。使用与生存显著相关的前 21 个差异表达基因构建预后模型。风险评分与生存呈负相关。富集分析显示,低风险组中富含免疫相关途径,该组还具有更多的免疫细胞浸润、更高的基质成分、更低的肿瘤纯度和更低的肿瘤异质性。最后,还观察到接受化疗和靶向治疗药物的高风险组和低风险组患者的半数最大抑制浓度也存在显著差异。我们研究中的这些发现可能为进一步研究和乳腺癌的个体化管理提供证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09ac/11537572/f203857c9f0d/medi-103-e40136-g001.jpg

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