标题:Genome-wide identification of FHL1 as a powerful prognostic candidate and potential therapeutic target in acute myeloid leukaemia
作者:Fu Y.; Xu M.; Cui Z.; Yang Z.; Zhang Z.; Yin X.; Huang X.; Zhou M.;等 更多
作者机构:[Fu, Y] Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China, School of Medicine, Shandong University, Jinan, Shando 更多
通讯作者:Chen, C(chency@sdu.edu.cn)
通讯作者地址:[Chen, C] Department of Hematology, Qilu Hospital of Shandong UniversityChina;
来源:EBioMedicine
出版年:2020
卷:52
DOI:10.1016/j.ebiom.2020.102664
关键词:Acute myeloid leukaemia; Cytarabine; FHL1; Prognosis; WGCNA
摘要:Background: Acute myeloid leukaemia (AML) is a malignant haematological tumour with high heterogeneity and mortality. A reliable prognostic assessment is critical for treatment strategies. However, the current prognostic evaluation system of AML is insufficient. Methods: Genome-wide univariate Cox regression analysis was performed on three independent AML datasets to screen for the prognostic-related genes. Kaplan–Meier survival analysis was employed to verify the efficacy of FHL1 in evaluating overall survival in 1298 de novo AML patients, 648 non-acute promyelocytic leukaemia AML patients and 407 cytogenetically normal AML patients; the data for some of these patients were also used for EFS and RFS validation. Multivariate Cox regression was performed to validate FHL1 as an independent prognostic indicator. WGCNA, GSEA, and gene correlation analysis were applied to explore the mechanism of FHL1 in AML. The synergistic cytocidal effect of FHL1 knockdown was verified in in vitro experiments. Findings: Comprehensive genome-wide analyses and large-sample validation showed that FHL1 is a powerful prognostic candidate for overall survival, event-free survival, and relapse-free survival in AML and is independent of prognosis-related clinical factors and genetic abnormalities. The molecular mechanism may occur through regulation of FHL1 in leukaemia stem cells, tumour-associated signalling pathways, and transmembrane transport of chemotherapeutic drugs. FHL1-targeted intervention enhances the sensitivity of AML cells to cytarabine. Interpretation: FHL1 may serve as an evaluation factor for clinical strategy selection, and its targeted intervention may be beneficial for chemotherapy in AML patients. © 2020 The Authors
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079426824&doi=10.1016%2fj.ebiom.2020.102664&partnerID=40&md5=d54af7a3edd40c010ceae3a030cec26d
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