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基于生物信息学分析和机器学习的免疫相关生物标志物预测乳腺癌的预后和免疫反应。

Immune-related biomarkers predict the prognosis and immune response of breast cancer based on bioinformatic analysis and machine learning.

机构信息

School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.

School of Mathematics and Statistics, Henan University of Science and Technology, Luoyang, China.

出版信息

Funct Integr Genomics. 2023 Jun 8;23(3):201. doi: 10.1007/s10142-023-01124-x.

Abstract

Breast cancer (BC) is the malignancy with the highest mortality rate among women, identification of immune-related biomarkers facilitates precise diagnosis and improvement of the survival rate in early-stage BC patients. 38 hub genes significantly positively correlated with tumor grade were identified based on weighted gene coexpression network analysis (WGCNA) by integrating the clinical traits and transcriptome analysis. Six candidate genes were screened from 38 hub genes basing on least absolute shrinkage and selection operator (LASSO)-Cox and random forest. Four upregulated genes (CDC20, CDCA5, TTK and UBE2C) were identified as biomarkers with the log-rank p < 0.05, in which high expression levels of them showed a poor overall survival (OS) and recurrence-free survival (RFS). A risk model was finally constructed using LASSO-Cox regression coefficients and it possessed superior capability to identify high risk patients and predict OS (p < 0.0001, AUC at 1-, 3- and 5-years are 0.81, 0.73 and 0.79, respectively). Decision curve analysis demonstrated risk score was the best prognostic predictor, and low risk represented a longer survival time and lower tumor grade. Importantly, multiple immune cell types and immunotherapy targets were observed increase in expression levels in high-risk group, most of which were significantly correlated with four genes. In summary, the immune-related biomarkers could accurately predict the prognosis and character the immune responses in BC patients. In addition, the risk model is conducive to the tiered diagnosis and treatment of BC patients.

摘要

乳腺癌(BC)是女性中死亡率最高的恶性肿瘤,鉴定免疫相关的生物标志物有助于早期 BC 患者的精确诊断和生存率的提高。通过整合临床特征和转录组分析,基于加权基因共表达网络分析(WGCNA),我们鉴定了 38 个与肿瘤分级显著正相关的枢纽基因。基于最小绝对收缩和选择算子(LASSO)-Cox 和随机森林,从 38 个枢纽基因中筛选出 6 个候选基因。有 4 个上调基因(CDC20、CDCA5、TTK 和 UBE2C)被鉴定为具有统计学意义的生物标志物(log-rank p < 0.05),它们的高表达水平显示出较差的总生存期(OS)和无复发生存期(RFS)。最后使用 LASSO-Cox 回归系数构建风险模型,该模型具有识别高危患者和预测 OS 的优异能力(p < 0.0001,1、3、5 年 AUC 分别为 0.81、0.73 和 0.79)。决策曲线分析表明风险评分是最佳预后预测指标,低危代表更长的生存时间和更低的肿瘤分级。重要的是,在高危组中观察到多种免疫细胞类型和免疫治疗靶点的表达水平增加,其中大多数与 4 个基因显著相关。总之,免疫相关的生物标志物可以准确预测 BC 患者的预后,并描绘免疫反应的特征。此外,该风险模型有助于对 BC 患者进行分层诊断和治疗。

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