单位：[1]Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[2]Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands[3]State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[4]Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, China[5]Department of Medicine, William Beaumont Hospital, Royal Oak, MI, USA[6]Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China[7]Department of Biomedical Sciences, University of Sassari, Sassari, Italy[8]Department of Operations and Information Management, China-Japan Friendship Hospital, Beijing, China[9]Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, China[10]Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, China
The mammalian target of rapamycin (mTOR) inhibitor, DNA damage inducible transcript 4 (DDIT4), has inducible expression in response to various cellular stresses. In multiple malignancies, studies have shown that DDIT4 participates in tumorigenesis and impacts patient survival. We aimed to study the prognostic value of DDIT4 in acute myeloid leukaemia (AML), which is currently unclear. Firstly, The Cancer Genome Atlas was screened for AML patients with complete clinical characteristics and DDIT4 expression data. A total of 155 patients were included and stratified according to the treatment modality and the median DDIT4 expression levels. High DDIT4 expressers had shorter overall survival (OS) and event-free survival (EFS) than the low expressers among the chemotherapy-only group (all P < .001); EFS and OS were similar in the high and low DDIT4 expressers of the allogeneic haematopoietic stem cell transplantation (allo-HSCT) group. Furthermore, in the DDIT4(high) group, patients treated with allo-HSCT had longer EFS and OS than those who received chemotherapy alone (all P < .01). In the DDIT4(low) group, OS and EFS were similar in different treatment groups. Secondly, we analysed two other cytogenetically normal AML (CN-AML) cohorts derived from the Gene Expression Omnibus database, which confirmed that high DDIT4 expression was associated with poorer survival. Gene Ontology (GO) enrichment analysis showed that the genes related to DDIT4 expression were mainly concentrated in the acute and chronic myeloid leukaemia signalling pathways. Collectively, our study indicates that high DDIT4 expression may serve as a poor prognostic factor for AML, but its prognostic effects could be outweighed by allo-HSCT.
基金：
China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2016M600443]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [U190310003, 61501519, 81500118, 81600089]
第一作者单位：[1]Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[2]Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands[3]State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[4]Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, China
通讯作者：
通讯机构：[1]Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[3]State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[9]Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, China[10]Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, China[*1]Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.[*2]Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, 100853, China
推荐引用方式(GB/T 7714)：
Zhiheng Cheng,Yifeng Dai,Yifan Pang,et al.Up-regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia[J].JOURNAL of CELLULAR and MOLECULAR MEDICINE.2020,24(1):1067-1075.doi:10.1111/jcmm.14831.
APA：
Zhiheng Cheng,Yifeng Dai,Yifan Pang,Yang Jiao,Yan Liu...&Lin Fu.(2020).Up-regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia.JOURNAL of CELLULAR and MOLECULAR MEDICINE,24,(1)
MLA：
Zhiheng Cheng,et al."Up-regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia".JOURNAL of CELLULAR and MOLECULAR MEDICINE 24..1(2020):1067-1075
