PMID- 31755224 OWN - NLM STAT- MEDLINE DCOM- 20210503 LR - 20210503 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 24 IP - 1 DP - 2020 Jan TI - Up-regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia. PG - 1067-1075 LID - 10.1111/jcmm.14831 [doi] AB - 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. CI - (c) 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Cheng, Zhiheng AU - Cheng Z AUID- ORCID: 0000-0001-8837-9542 AD - Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. AD - Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. AD - State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. AD - Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, China. FAU - Dai, Yifeng AU - Dai Y AUID- ORCID: 0000-0003-3507-7414 AD - Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. FAU - Pang, Yifan AU - Pang Y AD - Department of Medicine, William Beaumont Hospital, Royal Oak, MI, USA. FAU - Jiao, Yang AU - Jiao Y AUID- ORCID: 0000-0002-1077-6422 AD - Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China. FAU - Liu, Yan AU - Liu Y AD - Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, China. FAU - Cui, Longzhen AU - Cui L AD - Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, China. FAU - Quan, Liang AU - Quan L AD - Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. AD - State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Qian, Tingting AU - Qian T AD - Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. AD - State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Zeng, Tiansheng AU - Zeng T AD - Department of Biomedical Sciences, University of Sassari, Sassari, Italy. FAU - Si, Chaozeng AU - Si C AD - Department of Operations and Information Management, China-Japan Friendship Hospital, Beijing, China. FAU - Huang, Wenhui AU - Huang W AD - Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. AD - State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Chen, Jinghong AU - Chen J AD - State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Pang, Ying AU - Pang Y AD - Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Ye, Xu AU - Ye X AD - Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Shi, Jinlong AU - Shi J AD - Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, China. FAU - Fu, Lin AU - Fu L AUID- ORCID: 0000-0002-2416-7572 AD - Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. AD - State Key Laboratory of Respiratory Disease, Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. AD - Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191121 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Biomarkers, Tumor) RN - 0 (DDIT4 protein, human) RN - 0 (Transcription Factors) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Biomarkers, Tumor/*metabolism MH - Combined Modality Therapy MH - Female MH - Follow-Up Studies MH - Hematopoietic Stem Cell Transplantation/*mortality MH - Humans MH - Leukemia, Myeloid, Acute/metabolism/*mortality/pathology/therapy MH - Male MH - Middle Aged MH - Prognosis MH - Retrospective Studies MH - Survival Rate MH - Transcription Factors/genetics/*metabolism MH - Transplantation, Homologous PMC - PMC6933361 OTO - NOTNLM OT - DNA damage inducible transcript 4 OT - acute myeloid leukaemia OT - allogeneic haematopoietic stem cell transplantation OT - chemotherapy OT - prognosis COIS- The authors confirm that there are no conflicts of interest. EDAT- 2019/11/23 06:00 MHDA- 2021/05/04 06:00 PMCR- 2020/01/01 CRDT- 2019/11/23 06:00 PHST- 2019/07/02 00:00 [received] PHST- 2019/10/28 00:00 [revised] PHST- 2019/10/30 00:00 [accepted] PHST- 2019/11/23 06:00 [pubmed] PHST- 2021/05/04 06:00 [medline] PHST- 2019/11/23 06:00 [entrez] PHST- 2020/01/01 00:00 [pmc-release] AID - JCMM14831 [pii] AID - 10.1111/jcmm.14831 [doi] PST - ppublish SO - J Cell Mol Med. 2020 Jan;24(1):1067-1075. doi: 10.1111/jcmm.14831. Epub 2019 Nov 21.