基于铁死亡基因,对一种新的乳腺癌治疗靶点进行分析,并构建预后模型。
Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes.
发表日期:2023 Aug 24
作者:
Qi Li, Hengchen Liu, Yun Jin, Yuanquan Yu, Yihang Wang, Di Wu, Yinghao Guo, Longfu Xi, Dan Ye, Yanzhi Pan, Xiaoxiao Zhang, Jiangtao Li
来源:
COMPUTERS IN BIOLOGY AND MEDICINE
摘要:
乳腺癌是全球女性中最常见的恶性肿瘤,也是女性死亡的重要原因。目前针对乳腺癌患者的现有预后模型并不准确,因为乳腺癌对常用的抗肿瘤药物具有耐药性。铁过氧化物死亡(Ferroptosis)是一种依赖于铁积累和脂质过氧化的新型程序性细胞死亡机制。多项研究已经证实了铁过氧化物死亡在肿瘤调控中的作用,现在认为铁过氧化物死亡在乳腺癌发展中发挥着重要作用。目前,乳腺癌预后与铁过氧化物死亡相关基因表达之间的关联尚不明确。进一步探索这一研究领域可能优化对乳腺癌患者预后的评估和预测,并寻找新的治疗靶点。本研究从癌基因组图谱数据库(TCGA)和基因表达数据库(GEO)中评估了乳腺癌样本的临床因素和多个基因的表达情况。从差异表达基因中鉴定出11个与预后相关的基因(TP63、IFNG、MT3、ANO6、FLT3、PTGS2、SLC1A4、JUN、SLC7A5、CHAC1和TF),构建了一个具有良好预测能力的生存预测模型。KEGG途径分析显示,免疫相关途径是主要途径。ssGSEA分析显示,某些免疫相关细胞亚群(如CD8+T细胞和B细胞)的分布以及多个免疫基因(包括II型干扰素反应和APC抑制)的表达存在显著差异。此外,在乳腺癌中发现了与铁过氧化物死亡相关的10个免疫靶点:CD276、CD80、HHLA2、LILRA2、NCR3LG1、NECTIN3、PVR、SLAMF9、TNFSF4和BTN1A1。利用TCGA鉴定了与乳腺癌预后相关的新型铁过氧化物死亡基因,开发了一种可靠和准确的预后模型,并找到了与传统靶向药物不同的10个潜在治疗靶点,为改善乳腺癌患者的不良预后提供了参考。版权所有 © 2023 Elsevier Ltd.
Breast cancer, which is the most common malignant tumor among women worldwide and an important cause of death in women. The existing prognostic model for patients with breast cancer is not accurate as breast cancer is resistant to commonly used antitumor drugs. Ferroptosis is a novel mechanism of programmed cell death that depends on iron accumulation and lipid peroxidation. Various studies have confirmed the role of ferroptosis in tumor regulation and ferroptosis is now considered to play an important role in breast cancer development. At present, the association between breast cancer prognosis and ferroptosis-related gene expression remains unclear. Further exploration of this research area may optimize the evaluation and prediction of prognosis of patients with breast cancer and finding of new therapeutic targets. In this study, clinical factors and the expression of multiple genes were evaluated in breast cancer samples from the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database database. Eleven prognostication-related genes (TP63, IFNG, MT3, ANO6, FLT3, PTGS2, SLC1A4, JUN, SLC7A5, CHAC1, and TF) were identified from differentially expressed genes to construct a survival prediction model, which showed a good prediction ability. KEGG pathway analysis revealed that immune-related pathways were the primary pathways. ssGSEA analysis showed significant differences in the distribution of certain immune-related cell subsets, such as CD8+T cells and B cells, and in the expression of multiple immune genes, including type II IFN response and APC coinhibition. In addition, 10 immune targets related to ferroptosis in breast cancer were found: CD276, CD80, HHLA2, LILRA2, NCR3LG1, NECTIN3, PVR, SLAMF9,TNFSF4, and BTN1A1. Using TCGA, new ferroptosis genes related to breast cancer prognosis were identified, a new reliable and accurate prognosis model was developed, and 10 new potential therapeutic targets different from the traditional targeted drugs were identified to provide a reference for improving the poor prognosis of patients with breast cancer.Copyright © 2023. Published by Elsevier Ltd.