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通过单细胞测序分析构建与乳腺癌铜依赖性相关的预后模型。

Construction of a prognostic model related to copper dependence in breast cancer by single-cell sequencing analysis.

作者信息

Guan Xiao, Lu Na, Zhang Jianping

机构信息

Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Front Genet. 2022 Aug 23;13:949852. doi: 10.3389/fgene.2022.949852. eCollection 2022.

Abstract

To explore the clinical significance of copper-dependent-related genes (CDRG) in female breast cancer (BC). CDRG were obtained by single-cell analysis of the GSE168410 dataset in the Gene Expression Omnibus (GEO) database. According to a 1:1 ratio, the Cancer Genome Atlas (TCGA) cohort was separated into a training and a test cohort randomly. Based on the training cohort, the prognostic model was built using COX and Lasso regression. The test cohort was used to validate the model. The GSE20685 dataset and GSE20711 dataset were used as two external validation cohorts to further validate the prognostic model. According to the median risk score, patients were classified as high-risk or low-risk. Survival analysis, immune microenvironment analysis, drug sensitivity analysis, and nomogram analysis were used to evaluate the clinical importance of this prognostic model. 384 CDRG were obtained by single-cell analysis. According to the prognostic model, patients were classified as high-risk or low-risk in both cohorts. The high-risk group had a significantly worse prognosis. The area under the curve (AUC) of the model was around 0.7 in the four cohorts. The immunological microenvironment was examined for a possible link between risk score and immune cell infiltration. Veliparib, Selumetinib, Entinostat, and Palbociclib were found to be more sensitive medications for the high-risk group after drug sensitivity analysis. Our CDRG-based prognostic model can aid in the prediction of prognosis and treatment of BC patients.

摘要

探讨铜依赖性相关基因(CDRG)在女性乳腺癌(BC)中的临床意义。通过对基因表达综合数据库(GEO)中GSE168410数据集进行单细胞分析获得CDRG。按照1:1的比例,将癌症基因组图谱(TCGA)队列随机分为训练队列和测试队列。基于训练队列,使用COX和Lasso回归构建预后模型。测试队列用于验证该模型。GSE20685数据集和GSE20711数据集用作两个外部验证队列,以进一步验证预后模型。根据中位风险评分,将患者分为高危或低危。采用生存分析、免疫微环境分析、药物敏感性分析和列线图分析来评估该预后模型的临床重要性。通过单细胞分析获得384个CDRG。根据预后模型,两个队列中的患者均被分为高危或低危。高危组的预后明显更差。该模型在四个队列中的曲线下面积(AUC)约为0.7。对免疫微环境进行检查,以寻找风险评分与免疫细胞浸润之间的可能联系。药物敏感性分析后发现,维利帕尼、司美替尼、恩替诺特和帕博西尼对高危组更敏感。我们基于CDRG的预后模型有助于预测BC患者的预后和指导治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5781/9445252/834f8e2fbac1/fgene-13-949852-g001.jpg

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