{"title":"通过加权基因共表达网络分析确定急性髓性白血病中的关键基因和功能丰富的通路","authors":"Jimo Jian, Chenglu Yuan, Hongyuan Hao","doi":"10.1007/s13353-024-00881-0","DOIUrl":null,"url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is characterized by the uncontrolled proliferation of myeloid leukemia cells in the bone marrow and other hematopoietic tissues and is highly heterogeneous. While with the progress of sequencing technology, understanding of the AML-related biomarkers is still incomplete. The purpose of this study is to identify potential biomarkers for prognosis of AML. Based on WGCNA analysis of gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases were employed for investigating potential biomarkers for the prognosis of AML. This study screened a total of 6153 genes by analyzing various changes in 103 acute myeloid leukemia (AML) samples, including gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases. Moreover, seven AML-related co-expression modules were mined by WGCNA analysis, and twelve biomarkers associated with the AML prognosis were identified from each top 10 genes of the seven co-expression modules. The AML samples were then classified into two subgroups, the prognosis of which is significantly different, based on the expression of these twelve genes. The differentially expressed 7 genes of two subgroups (HOXB-AS3, HOXB3, SLC9C2, CPNE8, MEG8, S1PR5, MIR196B) are mainly involved in glucose metabolism, glutathione biosynthesis, small G protein-mediated signal transduction, and the Rap1 signaling pathway. With the utilization of WGCNA mining, seven gene co-expression modules were identified from the TCGA database, and there are unreported genes that may be potential driver genes of AML and may be the direction to identify the possible molecular signatures to predict survival of AML patients and help guide experiments for potential clinical drug targets.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identifying key genes and functionally enriched pathways in acute myeloid leukemia by weighted gene co-expression network analysis.\",\"authors\":\"Jimo Jian, Chenglu Yuan, Hongyuan Hao\",\"doi\":\"10.1007/s13353-024-00881-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Acute myeloid leukemia (AML) is characterized by the uncontrolled proliferation of myeloid leukemia cells in the bone marrow and other hematopoietic tissues and is highly heterogeneous. While with the progress of sequencing technology, understanding of the AML-related biomarkers is still incomplete. The purpose of this study is to identify potential biomarkers for prognosis of AML. Based on WGCNA analysis of gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases were employed for investigating potential biomarkers for the prognosis of AML. This study screened a total of 6153 genes by analyzing various changes in 103 acute myeloid leukemia (AML) samples, including gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases. Moreover, seven AML-related co-expression modules were mined by WGCNA analysis, and twelve biomarkers associated with the AML prognosis were identified from each top 10 genes of the seven co-expression modules. The AML samples were then classified into two subgroups, the prognosis of which is significantly different, based on the expression of these twelve genes. The differentially expressed 7 genes of two subgroups (HOXB-AS3, HOXB3, SLC9C2, CPNE8, MEG8, S1PR5, MIR196B) are mainly involved in glucose metabolism, glutathione biosynthesis, small G protein-mediated signal transduction, and the Rap1 signaling pathway. With the utilization of WGCNA mining, seven gene co-expression modules were identified from the TCGA database, and there are unreported genes that may be potential driver genes of AML and may be the direction to identify the possible molecular signatures to predict survival of AML patients and help guide experiments for potential clinical drug targets.</p>\",\"PeriodicalId\":14891,\"journal\":{\"name\":\"Journal of Applied Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Applied Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s13353-024-00881-0\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13353-024-00881-0","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
急性髓性白血病(AML)的特征是骨髓和其他造血组织中髓性白血病细胞不受控制地增殖,具有高度异质性。随着测序技术的进步,人们对急性髓细胞白血病相关生物标志物的了解仍不全面。本研究的目的是确定急性髓细胞性白血病预后的潜在生物标志物。本研究基于 WGCNA 对基因突变表达、甲基化水平分布、mRNA 表达的分析,并利用公共数据库中的 AML 相关基因来研究 AML 预后的潜在生物标志物。本研究通过分析103个急性髓性白血病样本的各种变化,包括基因突变表达、甲基化水平分布、mRNA表达以及公共数据库中的AML相关基因,共筛选出6153个基因。此外,还通过 WGCNA 分析挖掘出了 7 个与 AML 相关的共表达模块,并从 7 个共表达模块的前 10 个基因中发现了 12 个与 AML 预后相关的生物标志物。然后根据这十二个基因的表达情况,将急性髓细胞样本分为预后有显著差异的两个亚组。两个亚组中差异表达的 7 个基因(HOXB-AS3、HOXB3、SLC9C2、CPNE8、MEG8、S1PR5、MIR196B)主要参与葡萄糖代谢、谷胱甘肽生物合成、小 G 蛋白介导的信号转导和 Rap1 信号通路。通过WGCNA挖掘,从TCGA数据库中发现了7个基因共表达模块,其中有一些未报道的基因可能是急性髓细胞性白血病的潜在驱动基因,可作为鉴定可能的分子特征的方向,以预测急性髓细胞性白血病患者的生存率,并帮助指导潜在临床药物靶点的实验。
Identifying key genes and functionally enriched pathways in acute myeloid leukemia by weighted gene co-expression network analysis.
Acute myeloid leukemia (AML) is characterized by the uncontrolled proliferation of myeloid leukemia cells in the bone marrow and other hematopoietic tissues and is highly heterogeneous. While with the progress of sequencing technology, understanding of the AML-related biomarkers is still incomplete. The purpose of this study is to identify potential biomarkers for prognosis of AML. Based on WGCNA analysis of gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases were employed for investigating potential biomarkers for the prognosis of AML. This study screened a total of 6153 genes by analyzing various changes in 103 acute myeloid leukemia (AML) samples, including gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases. Moreover, seven AML-related co-expression modules were mined by WGCNA analysis, and twelve biomarkers associated with the AML prognosis were identified from each top 10 genes of the seven co-expression modules. The AML samples were then classified into two subgroups, the prognosis of which is significantly different, based on the expression of these twelve genes. The differentially expressed 7 genes of two subgroups (HOXB-AS3, HOXB3, SLC9C2, CPNE8, MEG8, S1PR5, MIR196B) are mainly involved in glucose metabolism, glutathione biosynthesis, small G protein-mediated signal transduction, and the Rap1 signaling pathway. With the utilization of WGCNA mining, seven gene co-expression modules were identified from the TCGA database, and there are unreported genes that may be potential driver genes of AML and may be the direction to identify the possible molecular signatures to predict survival of AML patients and help guide experiments for potential clinical drug targets.
期刊介绍:
The Journal of Applied Genetics is an international journal on genetics and genomics. It publishes peer-reviewed original papers, short communications (including case reports) and review articles focused on the research of applicative aspects of plant, human, animal and microbial genetics and genomics.