用于临床预测乳腺癌患者预后的内质网应激相关特征。

IF 3.1 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Enqi Qiao, Jiayi Ye, Kaiming Huang
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引用次数: 0

摘要

背景:内质网应激(ER应激)是乳腺癌发病过程中的一个重要事件。我们的目的是根据与ER应激相关的关键基因预测预后:方法:我们从 TCGA 数据库下载了乳腺癌病例的 RNA-seq 数据和临床信息。方法:我们从TCGA数据库中下载了乳腺癌病例的RNA-seq数据和临床信息,通过单变量Cox回归和最小绝对缩减和选择操作者(LASSO)化Cox比例危险度回归分析,共确定了4个与ER压力相关的基因。我们利用 Kaplan-Meier 曲线和随时间变化的接收者操作特征曲线(ROC)评估了 ER 压力模型的预测能力。此外,我们还验证了 4 个基因的表达及其与现实世界中临床乳腺癌病例的关系:结果:包括 RNF186、BCAP31、SERPINA1 和 TAPBP 在内的 4 个基因被确定为预后风险评分模型。在此基础上,我们发现低风险评分的乳腺癌患者生存率更高。此外,ER 压力模型的 AUC 曲线也显示出良好的诊断效果。风险评分与患者的年龄、T分期和临床分期有明显的相关性。构建了一个提名图来估计个体生存率。进一步的 GO 和 KEGG 分析表明,我们的模型与免疫浸润有关。高风险评分的乳腺癌患者通常伴有较差的免疫浸润。据预测,高危人群对维诺雷宾、多西他赛和顺铂更敏感。最后,我们利用 qRT-PCR 和免疫组化技术验证了四个特征基因的表达:我们的ER压力模型对乳腺癌患者进行了有价值的预测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An endoplasmic reticulum stress related signature for clinically predicting prognosis of breast cancer patients.

Background: Endoplasmic Reticulum Stress (ER stress) was an important event in the development of breast cancer. We aimed to predict prognosis based on ER stress related key genes.

Methods: Data of the RNA-seq and clinical information of breast cancer cases were downloaded from the TCGA database. A total of 4 genes related with ER stress was identified by the univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the ER stress model was evaluated by utilizing Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves. Moreover, we verified 4 genes expression and its relationship with clinical breast cancer cases in real-world.

Results: 4 genes including RNF186, BCAP31, SERPINA1, TAPBP were identified as a prognostic risk score model. Based on that, we found patients of breast cancer had a better survival with low-risk score. And also, ER stress model showed a good diagnostic efficacy with AUC curve. The risk score was significantly associated with patients' age, T stage and clinical stage. A nomogram was constructed to estimate individual survival. Further GO and KEGG analysis showed our model was related with immune infiltration. Patients of breast cancer with high-risk scores were usually accompanied with poor immune infiltration. It was predicted that high risk group was more sensitive to Vinorelbine, Docetaxel and Cisplatin. At last, we verified the expression of four signature genes using qRT-PCR and immunohistochemistry.

Conclusion: Our ER stress model performed a valuable prediction on breast cancer patients.

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来源期刊
Human molecular genetics
Human molecular genetics 生物-生化与分子生物学
CiteScore
6.90
自引率
2.90%
发文量
294
审稿时长
2-4 weeks
期刊介绍: Human Molecular Genetics concentrates on full-length research papers covering a wide range of topics in all aspects of human molecular genetics. These include: the molecular basis of human genetic disease developmental genetics cancer genetics neurogenetics chromosome and genome structure and function therapy of genetic disease stem cells in human genetic disease and therapy, including the application of iPS cells genome-wide association studies mouse and other models of human diseases functional genomics computational genomics In addition, the journal also publishes research on other model systems for the analysis of genes, especially when there is an obvious relevance to human genetics.
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