对乳腺癌中细胞周期相关基因表达的特征和肿瘤微环境浸润的表征及其治疗反应的研究。
Characterization of tumor microenvironment infiltration and therapeutic responses of cell cycle-related genes' signature in breast cancer.
发表日期:2023 Aug 04
作者:
Huacong Wu, Yutao Chen, Mengyi Li, Zijun Chen, Jie Liu, Guie Lai
来源:
Immunity & Ageing
摘要:
目前还不清楚细胞周期在乳腺癌(BC)中的作用。本研究旨在建立一个临床适用的预测模型,以预测BC患者的治疗反应和总体生存率。在肿瘤基因组图谱队列(n=1001)和基因表达数据总库队列(n=3265)中鉴定与细胞周期相关的基因(CCGs)。然后进行单变量和多变量Cox分析,基于CCGs开发一个图谱。验证图谱后,建立风险队列分层并进行预测值考察。最后,分析免疫细胞浸润和治疗反应。
根据15个CCG,鉴定出4个预后指标并输入图谱。根据校准曲线,图谱的估计值和观察值达到最佳一致性。随后,将患者分为两个风险队列,低风险患者的预测效果、免疫细胞浸润和总体生存率均更好。高风险BC患者的免疫检查点表达下调。此外,研究结果显示,多柔比星、紫杉醇、多塞唑、顺铂和以索非辛在高风险BC患者中具有更高的IC50值。
基于CCG的图谱可以评估BC的肿瘤免疫微环境调节和免疫治疗的治疗反应。此外,它还可能为BC中免疫微环境浸润的控制提供新的信息,并促进靶向免疫治疗的发展。©2023。作者授权Springer-Verlag GmbH Germany独家使用,Springer Nature的一部分。
It is unknown how the cell cycle plays a role in breast cancer (BC). This study aimed to establish a clinically applicable predictive model to predict the therapeutic responses and overall survival in BC patients.Cell cycle-related genes (CCGs) were identified within the Cancer Genome Atlas cohort (n is equal to 1001) and the Gene Expression Omnibus cohort (n is equal to 3265). An analysis of univariate and multivariate Cox was then conducted to develop a nomogram based on CCGs. After validating the nomogram, risk cohort stratification was established and the predictive value was examined. Finally, immune cell infiltration and therapeutic responses were analysed.Based on 15 CCGs, 4 prognostic predictors were identified and entered into the nomogram. According to the curves of calibration, the estimated and observed value of the nomogram is in optimal agreement. Subsequently, stratification into two risk cohorts showed that the predictive value, immune cell infiltration and overall survival were better among patients with low risk. Immune checkpoint expression in patients with BC at higher risk was downregulated. Furthermore, the results of the study revealed that doxorubicin, paclitaxel, docetaxel, cisplatin and vinorelbine all had higher IC50 values in patients with high-risk BC.The nomogram based on CCG could assess tumour immune micro-environment regulation and therapeutic responses of immunotherapy in BC. Moreover, it may provide novel information on the control of immune micro-environment infiltration in BC and aid in the development of targeted immunotherapy.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.