Novel molecular insights into pyroptosis in triple-negative breast cancer prognosis and immunotherapy

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2023-12-02 DOI:10.1002/jgm.3645

Bin Yu, Junjie Luo, Yifei Yang, Ke Zhen, Binjie Shen

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引用次数: 0

Abstract

Background

Patients with triple-negative breast cancer (TNBC) often have a poor prognostic outcome. Current treatment strategies cannot benefit all TNBC patients. Previous findings suggested pyroptosis as a novel target for suppressing cancer development, although the relationship between TNBC and pyroptosis-related genes (PRGs) was still unclear.

Methods

Gene expression data and clinical follow-up of TNBC patients were collected from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). PRGs were screened using weighted gene co-expression network analysis. Cox regression analysis and the least absolute shrinkage and selection operator (i.e. LASSO) technique were applied to construct a pyroptosis-related prognostic risk score (PPRS) model, which was further combined with the clinicopathological characteristics of TNBC patients to develop a survival decision tree and a nomogram. The model was used to calculate the PPRS, and then the overall survival, immune infiltration, immunotherapy response and drug sensitivity of TNBC patients were analyzed based on the PPRS.

Results

The PPRS model was closely related to clinicopathological features and can independently and accurately predict the prognosis of TNBC. According to normalized PPRS, patients in different cohorts were divided into two groups. Compared with the high-PPRS group, the low-PPRS group had significantly higher ESTIMATE (i.e. Estimation of STromal and Immune cells in MAlignantTumours using Expression data) score, immune score and stromal score, and it also had overexpressed immune checkpoints and significantly reduced Tumor Immune Dysfunction and Exclusion (TIDE) score, as well as higher sensitivity to paclitaxel, veliparib, olaparib and talazoparib. A decision tree and nomogram based on PPRS and clinical characteristics can improve the prognosis stratification and survival prediction for TNBC patients.

Conclusions

A PPRS model was developed to predict TNBC patients' immune characteristics and response to immunotherapy, chemotherapy and targeted therapy, as well as their survival outcomes.

Abstract Image

查看原文本刊更多论文

三阴性乳腺癌预后和免疫治疗中焦亡的新分子见解。

背景:三阴性乳腺癌(TNBC)患者通常预后较差。目前的治疗策略不能使所有TNBC患者受益。先前的研究结果表明，虽然TNBC与焦亡相关基因(PRGs)之间的关系尚不清楚，但焦亡是抑制癌症发展的新靶点。方法:从国际乳腺癌分子分类联盟(METABRIC)和基因表达综合数据库(GEO)收集TNBC患者的基因表达数据和临床随访。采用加权基因共表达网络分析筛选PRGs。采用Cox回归分析和最小绝对收缩和选择算子(LASSO)技术构建热休克相关预后风险评分(PPRS)模型，并结合TNBC患者的临床病理特征，形成生存决策树和nomogram。利用该模型计算PPRS，基于PPRS分析TNBC患者的总生存率、免疫浸润、免疫治疗反应和药物敏感性。结果:PPRS模型与临床病理特征密切相关，能独立准确预测TNBC的预后。根据标准化PPRS，将不同队列的患者分为两组。与高pprs组相比，低pprs组的ESTIMATE(利用表达数据估计恶性肿瘤基质和免疫细胞)评分、免疫评分和基质评分均显著升高，免疫检查点过表达，肿瘤免疫功能障碍和排斥(TIDE)评分显著降低，对紫杉醇、维利帕尼、奥拉帕尼和塔拉唑帕尼的敏感性更高。基于PPRS和临床特征的决策树和nomogram可以改善TNBC患者的预后分层和生存预测。结论:建立了PPRS模型，预测TNBC患者的免疫特征、免疫治疗、化疗和靶向治疗的反应以及生存结局。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.