Identification and validation of three tumor suppressors associated with the immune response of acute myeloid leukemia.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-09-16 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1652142

Yueyuan Pan, Guocai Wu, Chenchen Liu, Minggui Chen, Tian Xia, Yonghua Ma, Zhigang Yang, Ruiting Wen

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引用次数: 0

Abstract

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder marked by irregular expansion and maturation, giving rise to the aggregation of immature myeloid precursor cells. Although most patients achieve remission with initial treatment, the majority of relapses lead to poorer overall survival. The bone marrow (BM) immune microenvironment has been proven to significantly affect the progression of AML. However, the mechanisms that cause the imbalance of immune cell subsets and phenotypes remain partially obscure. Therefore, this research sought to explore the immune-regulatory genes and to determine their role in AML.

Methods: Differentially expressed genes (DEGs) were obtained through differential analysis of the AML cohort. Enrichment analyses were applied to explore their biological functions. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify the key module of AML. ROC curve analysis was performed to identify hub genes with good predictive power. CIBERSORT and the ESTIMATE algorithm were used to assess the correlation between hub genes and the immune microenvironment of AML. The impact of hub gene expression on the prognosis of AML was verified through prognostic traits and clinical samples.

Results: Through differential analysis and WGCNA, seven genes were identified as markedly related to the development of AML. By mapping ROC curves, three hub genes were verified: CCR7, SLC16A6, and MS4A1, which have high diagnostic value for AML. Additionally, an imbalanced immune microenvironment was found to be common in AML. Three hub genes were significantly associated with immune components, including immune cells and immunomodulatory factors. Ultimately, through the validation of clinical samples and the analysis of prognostic characteristics, three genes were confirmed to be reduced in AML patients, and their high expression suggested a favorable prognosis.

Conclusion: Our study identified and validated the efficacy of SLC16A6, CCR7, and MS4A1 as tumor suppressors implicated in AML progression and related to immune cell infiltration.

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三种与急性髓性白血病免疫应答相关的肿瘤抑制因子的鉴定和验证。

背景：急性髓系白血病（AML）是一种异质性疾病，其特征是不规则扩张和成熟，引起未成熟髓系前体细胞聚集。虽然大多数患者通过初始治疗获得缓解，但大多数复发导致总生存期较差。骨髓（BM）免疫微环境已被证明对AML的进展有显著影响。然而，导致免疫细胞亚群和表型失衡的机制仍然部分不清楚。因此，本研究试图探索免疫调节基因并确定其在AML中的作用。方法：通过AML队列的差异分析获得差异表达基因（DEGs）。富集分析对其生物学功能进行了研究。采用加权基因共表达网络分析（WGCNA）鉴定AML的关键模块。ROC曲线分析鉴定出预测能力较好的枢纽基因。利用CIBERSORT和ESTIMATE算法评估中枢基因与AML免疫微环境的相关性。通过预后特征和临床样本验证hub基因表达对AML预后的影响。结果：通过差异分析和WGCNA，鉴定出7个基因与AML的发展显著相关。通过绘制ROC曲线，验证了CCR7、SLC16A6和MS4A1三个枢纽基因，它们对AML具有较高的诊断价值。此外，在AML中发现免疫微环境失衡是常见的。三个枢纽基因与免疫成分，包括免疫细胞和免疫调节因子显著相关。最终，通过对临床样本的验证和对预后特征的分析，确认了AML患者中有3个基因的减少，它们的高表达提示预后良好。结论：我们的研究确定并验证了SLC16A6、CCR7和MS4A1作为肿瘤抑制因子的有效性，这些抑制因子参与AML的进展并与免疫细胞浸润相关。

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

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.