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急性髓系白血病中表达的临床及预后相关性。

Clinical and prognostic relevance of expression in acute myeloid leukemia.

作者信息

Wang Shi-Sen, Xu Zi-Jun, Jin Ye, Ma Ji-Chun, Xia Pei-Hui, Wen Xiangmei, Mao Zhen-Wei, Lin Jiang, Qian Jun

机构信息

Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

出版信息

PeerJ. 2021 Jul 20;9:e11820. doi: 10.7717/peerj.11820. eCollection 2021.

Abstract

BACKGROUND

Accumulating studies have been made to understand the association between chemokine ligand-12 ()/ chemokine receptor 4 () and acute myeloid leukemia (AML). However, large-scale data analysis of potential relationship between and AML remains insufficient.

METHODS

We collected abundant expression data and AML samples from several publicly available datasets. The CIBERSORT algorithm was used to quantify immune cell fractions and the online website of STRING was utilized for gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The statistical analysis and graphical work were mainly performed via the R software.

RESULTS

expression was extremely down-regulated in AML. Clinically, low expression was correlated with higher white blood cells (WBCs) ( < 0.0001), more blasts in bone marrow (BM) ( < 0.001) and peripheral blood (PB) ( < 0.0001), -internal tandem duplications (-ITD) ( = 0.010) and mutations ( = 0.015). More importantly, reduced expression predicted worse overall survival (OS) and event-free survival (EFS) in all AML, non-M3-AML, and cytogenetically normal (CN)-AML patients in three independent cohorts. As for immune cell infiltration, high expressed groups tended to harbor more memory B cells and plasma cells infiltration while low expressed groups exhibited more eosinophils infiltration. GO enrichment and KEGG pathways analysis revealed the potential biological progress the gene participating in.

CONCLUSIONS

is significantly down-regulated in AML and low expression is an independent and poor predictor of AML prognosis. expression level correlates with clinical and immune characteristics of AML, which could provide potential assistance for treatment. Prospective studies are needed to further validate the impact of expression before routine clinical application in AML.

摘要

背景

为了解趋化因子配体12(CXCL12)/趋化因子受体4(CXCR4)与急性髓系白血病(AML)之间的关联,已经开展了越来越多的研究。然而,关于CXCL12与AML潜在关系的大规模数据分析仍然不足。

方法

我们从几个公开可用的数据集中收集了丰富的CXCL12表达数据和AML样本。使用CIBERSORT算法量化免疫细胞分数,并利用STRING在线网站进行基因本体论(GO)富集和京都基因与基因组百科全书(KEGG)分析。统计分析和图形工作主要通过R软件进行。

结果

CXCL12在AML中表达极度下调。临床上,低CXCL12表达与较高的白细胞(WBC)(P<0.0001)、骨髓(BM)中更多的原始细胞(P<0.001)和外周血(PB)中更多的原始细胞(P<0.0001)、FLT3-内部串联重复(FLT3-ITD)(P = 0.010)以及NPM1突变(P = 0.015)相关。更重要的是,在三个独立队列中,CXCL12表达降低预示着所有AML、非M3-AML和细胞遗传学正常(CN)-AML患者的总生存期(OS)和无事件生存期(EFS)更差。至于免疫细胞浸润,高CXCL12表达组倾向于有更多记忆B细胞和浆细胞浸润,而低CXCL12表达组表现出更多嗜酸性粒细胞浸润。GO富集和KEGG通路分析揭示了该基因参与的潜在生物学过程。

结论

CXCL12在AML中显著下调,低CXCL12表达是AML预后的独立不良预测指标。CXCL12表达水平与AML的临床和免疫特征相关,可为治疗提供潜在帮助。在AML的常规临床应用之前,需要进行前瞻性研究以进一步验证CXCL12表达的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e94/8300536/1f93ac686b03/peerj-09-11820-g001.jpg

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