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基因表达升高是非M3型急性髓系白血病预后不良的一个预测指标。

Elevated gene expression is a predictor of poor prognosis in non-M3 acute myeloid leukemia.

作者信息

Gu Siyu, Zi Jie, Han Qi, Song Chunhua, Ge Zheng

机构信息

1Department of Hematology, Zhongda Hospital, School of Medicine, Southeast University, Institute of Hematology Southeast University, No. 87, Dingjiaqiao, Gulou District, Nanjing, 210009 Jiangsu China.

2Hershey Medical Center, Pennsylvania State University Medical College, Hershey, PA17033 USA.

出版信息

Cancer Cell Int. 2020 May 4;20:146. doi: 10.1186/s12935-020-01213-y. eCollection 2020.

Abstract

BACKGROUND

We used bioinformatic tools to dichotomize 157 non-M3 AML patients from the TCGA dataset based on the presence or absence of mutations, and screened out a key gene related to mutation for future analysis.

METHODS

DEGs were analyzed by R package "DESeq2" and then run GSEA, GO enrichment, KEGG pathway and PPI network. Hub genes were selected out according to MCC. Log-rank (Mantel-Cox) test was used for survival analysis. Mann-Whitney U's nonparametric t test and Fisher's exact test was used for continuous and categorical variables respectively. value< 0.05 was considered to be statistical significance.

RESULTS

was final screened out as a key gene. Besides mutation (= 0.0118), high was also associated with mutation (= 0.0102) and mutation (= 0.0024). Elevated was significantly related with intermediate (= 0.0004) and poor (= 0.0011) risk stratification as well as relapse statute (= 0.0099). Patients with elevated expression had significantly shorter overall survival (median survival: 2.35 months vs. 21 months, < 0.0001). Based on our clinical center data, expression was significantly higher in non-M3 AML patients than HDs (= 0.0377) and MDS patients (EB-1, 2; = 0.0017).

CONCLUSIONS

Elevated expression was associated with , mutation as well as poor clinical outcome. expression was significantly higher in non-M3 AML patients than HDs and MDS (EB-1, 2) patients. is need for future functional and mechanistic studies to investigate the role in non-M3 AML.

摘要

背景

我们使用生物信息学工具根据157例非M3急性髓系白血病(AML)患者是否存在突变对来自TCGA数据集的患者进行二分法分类,并筛选出一个与突变相关的关键基因以供未来分析。

方法

通过R包“DESeq2”分析差异表达基因(DEGs),然后进行基因集富集分析(GSEA)、基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)通路分析和蛋白质-蛋白质相互作用(PPI)网络分析。根据最大团中心性(MCC)选择枢纽基因。采用对数秩(Mantel-Cox)检验进行生存分析。分别对连续变量和分类变量采用曼-惠特尼U非参数t检验和费舍尔精确检验。P值<0.05被认为具有统计学意义。

结果

最终筛选出作为关键基因。除了突变(P = 0.0118)外,高表达还与突变(P = 0.0102)和突变(P = 0.0024)相关。升高与中危(P = 0.0004)和高危(P = 0.0011)风险分层以及复发状态(P = 0.0099)显著相关。表达升高的患者总生存期显著缩短(中位生存期:2.35个月对21个月,P < 0.0001)。基于我们临床中心的数据,非M3 AML患者中的表达显著高于健康对照(P = 0.0377)和骨髓增生异常综合征(MDS)患者(EB-1、2;P = 0.0017)。

结论

表达升高与、突变以及不良临床结局相关。非M3 AML患者中的表达显著高于健康对照和MDS(EB-1、2)患者。需要进一步进行功能和机制研究以探究在非M3 AML中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c20/7197135/1a95b107b1c8/12935_2020_1213_Fig1_HTML.jpg

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