A novel molecular classification based on efferocytosis-related genes for predicting clinical outcome and treatment response in acute myeloid leukemia.

IF 4.8 3区 医学 Q2 CELL BIOLOGY
Inflammation Research Pub Date : 2024-11-01 Epub Date: 2024-09-02 DOI:10.1007/s00011-024-01938-w
Fangmin Zhong, Fangyi Yao, Qin Bai, Jing Liu, Xiaolin Li, Bo Huang, Xiaozhong Wang
{"title":"A novel molecular classification based on efferocytosis-related genes for predicting clinical outcome and treatment response in acute myeloid leukemia.","authors":"Fangmin Zhong, Fangyi Yao, Qin Bai, Jing Liu, Xiaolin Li, Bo Huang, Xiaozhong Wang","doi":"10.1007/s00011-024-01938-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that macrophage-mediated efferocytosis is involved in immunosuppression in acute myeloid leukemia (AML). However, the regulatory role of efferocytosis in AML remains unclear and needs further elucidation.</p><p><strong>Methods: </strong>We first identified the key efferocytosis-related genes (ERGs) based on the expression matrix. Efferocytosis-related molecular subtypes were obtained by consensus clustering algorithm. Differences in immune landscape and biological processes among molecular subtypes were further evaluated. The efferocytosis score model was constructed to quantify molecular subtypes and evaluate its value in prognosis prediction and treatment decision-making in AML.</p><p><strong>Results: </strong>Three distinct efferocytosis-related molecular subtypes were identified and divided into immune activation, immune desert, and immunosuppression subtypes based on the characteristics of the immune landscape. We evaluated the differences in clinical and biological features among different molecular subtypes, and the construction of an efferocytosis score model can effectively quantify the subtypes. A low efferocytosis score is associated with immune activation and reduced mutation frequency, and patients have a better prognosis. A high efferocytosis score reflects immune exhaustion, increased activity of tumor marker pathways, and poor prognosis. The prognostic predictive value of the efferocytosis score model was confirmed in six AML cohorts. Patients exhibiting high efferocytosis scores may derive therapeutic benefits from anti-PD-1 immunotherapy, whereas those with low efferocytosis scores tend to exhibit greater sensitivity towards chemotherapy. Analysis of treatment data in ex vivo AML cells revealed a group of drugs with significant differences in sensitivity between different efferocytosis score groups. Finally, we validated model gene expression in a clinical cohort.</p><p><strong>Conclusions: </strong>This study reveals that efferocytosis plays a non-negligible role in shaping the diversity and complexity of the AML immune microenvironment. Assessing the individual efferocytosis-related molecular subtype in individuals will help to enhance our understanding of the characterization of the AML immune landscape and guide the establishment of more effective clinical treatment strategies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00011-024-01938-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Previous studies have shown that macrophage-mediated efferocytosis is involved in immunosuppression in acute myeloid leukemia (AML). However, the regulatory role of efferocytosis in AML remains unclear and needs further elucidation.

Methods: We first identified the key efferocytosis-related genes (ERGs) based on the expression matrix. Efferocytosis-related molecular subtypes were obtained by consensus clustering algorithm. Differences in immune landscape and biological processes among molecular subtypes were further evaluated. The efferocytosis score model was constructed to quantify molecular subtypes and evaluate its value in prognosis prediction and treatment decision-making in AML.

Results: Three distinct efferocytosis-related molecular subtypes were identified and divided into immune activation, immune desert, and immunosuppression subtypes based on the characteristics of the immune landscape. We evaluated the differences in clinical and biological features among different molecular subtypes, and the construction of an efferocytosis score model can effectively quantify the subtypes. A low efferocytosis score is associated with immune activation and reduced mutation frequency, and patients have a better prognosis. A high efferocytosis score reflects immune exhaustion, increased activity of tumor marker pathways, and poor prognosis. The prognostic predictive value of the efferocytosis score model was confirmed in six AML cohorts. Patients exhibiting high efferocytosis scores may derive therapeutic benefits from anti-PD-1 immunotherapy, whereas those with low efferocytosis scores tend to exhibit greater sensitivity towards chemotherapy. Analysis of treatment data in ex vivo AML cells revealed a group of drugs with significant differences in sensitivity between different efferocytosis score groups. Finally, we validated model gene expression in a clinical cohort.

Conclusions: This study reveals that efferocytosis plays a non-negligible role in shaping the diversity and complexity of the AML immune microenvironment. Assessing the individual efferocytosis-related molecular subtype in individuals will help to enhance our understanding of the characterization of the AML immune landscape and guide the establishment of more effective clinical treatment strategies.

Abstract Image

基于流出细胞相关基因的新型分子分类法,用于预测急性髓性白血病的临床结果和治疗反应。
背景:先前的研究表明,巨噬细胞介导的流出细胞增多参与了急性髓性白血病(AML)的免疫抑制。然而,流出细胞在急性髓性白血病中的调控作用仍不清楚,需要进一步阐明:方法:我们首先根据表达矩阵确定了与排泄相关的关键基因(ERGs)。方法:我们首先根据表达矩阵确定了与胞吐相关的关键基因(ERGs),然后通过共识聚类算法获得了与胞吐相关的分子亚型。进一步评估了不同分子亚型在免疫格局和生物过程方面的差异。结果发现,有三种截然不同的细胞外增殖相关分子亚型,它们分别是:(1) 细胞外增殖相关分子亚型;(2) 细胞外增殖相关分子亚型;(3) 细胞外增殖相关分子亚型:结果:根据免疫景观的特征,确定了三种不同的与流出相关的分子亚型,并将其分为免疫激活亚型、免疫荒漠亚型和免疫抑制亚型。我们评估了不同分子亚型在临床和生物学特征上的差异,并构建了一个能有效量化亚型的耗竭评分模型。流出率得分低与免疫激活和突变频率降低有关,患者的预后较好。流出率得分高则反映免疫耗竭、肿瘤标志物通路活性增强,预后较差。在六个急性髓细胞性白血病队列中证实了流出细胞增多评分模型的预后预测价值。表现出高流出率评分的患者可能会从抗PD-1免疫疗法中获益,而流出率评分低的患者往往对化疗更敏感。对体内外急性髓细胞治疗数据的分析表明,一组药物在不同细胞外吞噬分数组之间的敏感性存在显著差异。最后,我们在临床队列中验证了模型基因表达:本研究揭示了流出细胞在形成急性髓细胞性白血病免疫微环境的多样性和复杂性方面发挥着不可忽视的作用。评估个体中与流出相关的分子亚型将有助于加深我们对急性髓细胞性白血病免疫环境特征的理解,并指导制定更有效的临床治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信