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一种与急性髓系白血病的免疫状态和预后相关的炎症反应相关基因特征。

An inflammatory response-related gene signature associated with immune status and prognosis of acute myeloid leukemia.

作者信息

Wu Xin, Li Shiqin, Chen Dongjie, Zheng Guiping, Zhang Zhaohua, Li Zian, Sun Xiaoying, Zhao Qiangqiang, Xu Jingjuan

机构信息

Department of Spine Surgery, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.

Department of Cell Biology, School of Life Sciences, Central South University Changsha 410013, Hunan, China.

出版信息

Am J Transl Res. 2022 Jul 15;14(7):4898-4917. eCollection 2022.

Abstract

OBJECTIVE

To determine the prognostic significance of inflammatory response-associated genes in acute myeloid leukemia (AML).

METHODS

Transcriptomic profiles and related clinical information of AML patients were acquired from a public database. To establish a multi-gene prognosis signature, we performed least absolute shrinkage and selection operator Cox analysis for the TCGA cohort and evaluated the ICGC cohort for verification. Subsequently, Kaplan-Meier analysis was carried out to compare the overall survival (OS) rates between high- and low-risk groups. Biological function and single-sample gene set enrichment (ssGSEA) analyses were employed to investigate the association of risk score with immune status and the tumor microenvironment. Prognostic gene expression levels in AML samples and normal controls were confirmed by qRT-PCR and immunofluorescence.

RESULTS

We identified a potential inflammatory response-related signature comprising 11 differentially expressed genes, including ACVR2A, CCL22, EBI3, EDN1, FFAR2, HRH1, ICOSLG, IL-10, INHBA, ITGB3, and LAMP3, and found that AML patients with high expression levels in the high-risk group had poor OS rates. Biological function analyses revealed that prognostic genes mainly participated in inflammation and immunity signaling pathways. Analyses of cancer-infiltrating immunocytes indicated that in high-risk patients, the immune suppressive microenvironment was significantly affected. The expression of the inflammation reaction-associated signature was found to be associated with susceptibility to chemotherapy. There was a significant difference in prognostic gene expression between AML and control tissues.

CONCLUSION

A novel inflammatory response-related signature was developed with 11 candidate genes to predict prognosis and immune status in AML patients.

摘要

目的

确定炎症反应相关基因在急性髓系白血病(AML)中的预后意义。

方法

从公共数据库获取AML患者的转录组图谱和相关临床信息。为建立多基因预后特征,我们对TCGA队列进行了最小绝对收缩和选择算子Cox分析,并评估ICGC队列以进行验证。随后,进行Kaplan-Meier分析以比较高风险组和低风险组之间的总生存率(OS)。采用生物学功能和单样本基因集富集(ssGSEA)分析来研究风险评分与免疫状态和肿瘤微环境的关联。通过qRT-PCR和免疫荧光确认AML样本和正常对照中预后基因的表达水平。

结果

我们鉴定出一个由11个差异表达基因组成的潜在炎症反应相关特征,包括ACVR2A、CCL22、EBI3、EDN1、FFAR2、HRH1、ICOSLG、IL-10、INHBA、ITGB3和LAMP3,并发现高风险组中表达水平高的AML患者OS率较差。生物学功能分析表明,预后基因主要参与炎症和免疫信号通路。对癌症浸润免疫细胞的分析表明,在高风险患者中,免疫抑制微环境受到显著影响。发现炎症反应相关特征的表达与化疗敏感性相关。AML组织和对照组织之间的预后基因表达存在显著差异。

结论

开发了一种由11个候选基因组成的新型炎症反应相关特征,用于预测AML患者的预后和免疫状态。

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